Structure–function coupling reveals the brain hierarchical structure dysfunction in Alzheimer's disease: A multicenter study

Abstract BACKGROUND Alzheimer's disease (AD) is a neurodegenerative condition characterized by cognitive decline. To date, the specific dysfunction in the brain's hierarchical structure in AD remains unclear. METHODS We introduced the structural decoupling index (SDI), based on a multi‐site data set comprising functional and diffusion‐weighted magnetic resonance imaging data from 793 subjects, to assess their brain hierarchy. RESULTS Compared to normal controls (NCs), individuals with AD exhibited increased SDI within the posterior superior temporal sulcus, insular gyrus, precuneus, hippocampus, amygdala, postcentral gyrus, and cingulate gyrus; meanwhile, the patients with AD demonstrated decreased SDI in the frontal lobe. The SDI in those regions also showed a significant correlation with cognitive ability. Moreover, the SDI was a robust AD neuroimaging biomarker capable of accurately distinguishing diagnostic status (area under the curve [AUC] = 0.86). DISCUSSION Our findings revealed the dysfunction of the brain's hierarchical structure in AD. Furthermore, the SDI could serve as a promising neuroimaging biomarker for AD. Highlights This study utilized multi‐center, multi‐modal data from East Asian populations. We found an increased spatial gradient of the structure decoupling index (SDI) from sensory–motor to higher‐order cognitive regions. Changes in SDI are associated with energy metabolism and mitochondria. SDI can identify Alzheimer's disease (AD) and further uncover the disease mechanisms of AD.