Functional gradients reveal altered functional segregation in patients with amnestic mild cognitive impairment and Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) are associated with disrupted functional organization in brain networks, yet the finer changes in the topological organization in aMCI and AD remain to be investigated. Connectome gradients are a new tool representing brain functional topological organization in a low-dimensional space to smoothly capture the human macroscale hierarchy.MethodsHere, we examined altered topological organization in aMCI and AD by connectome gradient mapping. We further quantified functional segregation by gradient dispersion. Then, we systematically compared the alterations observed in aMCI and AD patients with those in normal controls (NCs) in a two-dimensional functional gradient space from both the whole-brain level and module level.ResultsCompared with NCs, the first gradient, which described the neocortical hierarchy from unimodal to transmodal regions, showed a distributed and significant suppression in AD patients, while abnormalities were only limited to local regions in aMCI patients. The second gradient showed a decreased pattern in the somatomotor module in both aMCI and AD patients. Furthermore, gradient dispersion showed significant decreases in AD patients at both the global level and module level, whereas this alteration was limited only to limbic areas in aMCI. Notably, we demonstrated that suppressed gradient dispersion in aMCI and AD patients was associated with cognitive scores.ConclusionsChanges in functional gradients could reflect different degrees of altered brain network segregation in aMCI and AD. These findings provide new evidence for altered brain hierarchy in aMCI and AD, which strengthens our understanding of the progressive mechanism of cognitive decline.