Brain network hierarchy reorganization in Alzheimer's disease: A resting-state functional magnetic resonance imaging...

Hierarchy is a fundamental organizational principle of the human brain network. Whether and how the network hierarchy changes in Alzheimer's disease (AD) remains unclear. To explore brain network hierarchy alterations in AD and their clinical relevance. Forty-nine healthy controls (HCs), 49 patients with mild cognitive impairment (MCI), and 49 patients with AD were included. The brain network hierarchy of each group was depicted by connectome gradient analyses. We assessed the network hierarchy changes by comparing the gradient values in each network across the AD, MCI, and HC groups. Whole-brain voxel-level gradient values were compared across the AD, MCI, and HC groups to identify abnormal brain regions. Finally, we examined the relationships between altered gradient values and clinical features. In the secondary gradient, the posterior default mode network (DMN) gradient values decreased significantly in patients with AD compared with HCs. Regionally, compared with HCs, both MCI and AD groups showed that most of the brain regions with increased gradient values were located in anterior DMN, while most of the brain regions with decreased gradient values were located in posterior DMN. The decrease of gradients in the left middle occipital gyrus was associated with better logical memory performance. The increase of gradients in the right middle frontal gyrus was associated with lower rates of dementia. The network hierarchy changed characteristically in patients with AD and was closely related to memory function and disease severity. These results provide a novel view for further understanding the underlying neuro-mechanisms of AD.