Distinct Profiles of Functional Connectivity Density Aberrance in Alzheimer's Disease and Mild Cognitive Impairment

Introduction: Investigating the neuroimaging changes from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is of great significance. However, the details about the distinct functional characteristics of AD and MCI remain unknown.

Methods: In this study, we investigated distinct profiles of functional connectivity density (FCD) differences between AD and MCI compared with the normal population, aiming to depict the progressive brain changes from MCI to AD. As a data-driven method, FCD measures the profiles of FC for the given voxel at different scales. Resting-state functional magnetic resonance imaging (fMRI) images were obtained from patients with AD and MCI and matched healthy controls (HCs). One-way ANCOVA was used to investigate (global, long-range, and local) FCD differences among the three groups followed by post-hoc analysis controlling age, sex, and head motion.

Results: The three groups exhibited significant global FCD differences in the superior frontal gyrus. The post-hoc results further showed that patients with AD had a significant increase in global FCD values than those with MCI and HCs. Patients with MCI exhibited an increased trend compared with HCs. We further identified brain regions contributing to the observed global FCD differences by conducting seed-based FC analysis. We also identified that the observed global FCD differences were the additive effects of altered FC between the superior frontal gyrus and the posterior default model network.

Discussion: These results depicted the global information communication capability impairment in AD and MCI providing a new insight into the progressive brain changes from MCI to AD.