Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline

Subjective cognitive decline (SCD) is considered the earliest stage of the clinical manifestations of the continuous progression of Alzheimer's Disease (AD). Previous studies have suggested that multimodal brain networks play an important role in the early diagnosis and mechanisms underlying SCD. However, most of the previous studies focused on a single modality, and lacked correlation analysis between different modal biomarkers and brain regions. In order to further explore the specific characteristic of the multimodal brain networks in the stage of SCD, 22 individuals with SCD and 20 matched healthy controls (HCs) were recruited in the present study. We constructed the individual morphological, structural and functional brain networks based on 3D-T1 structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. A t-test was used to select the connections with significant difference, and a multi-kernel support vector machine (MK-SVM) was applied to combine the selected multimodal connections to distinguish SCD from HCs. Moreover, we further identified the consensus connections of brain networks as the most discriminative features to explore the pathological mechanisms and potential biomarkers associated with SCD. Our results shown that the combination of three modal connections using MK-SVM achieved the best classification performance, with an accuracy of 92.68%, sensitivity of 95.00%, and specificity of 90.48%. Furthermore, the consensus connections and hub nodes based on the morphological, structural, and functional networks identified in our study exhibited abnormal cortical-subcortical connections in individuals with SCD. In addition, the functional networks presented more discriminative connections and hubs in the cortical-subcortical regions, and were found to perform better in distinguishing SCD from HCs. Therefore, our findings highlight the role of the cortical-subcortical circuit in individuals with SCD from the perspective of a multimodal brain network, providing potential biomarkers for the diagnosis and prediction of the preclinical stage of AD.