Longitudinal Alteration of Amygdalar Functional Connectivity in Mild Cognitive Impairment Subjects Revealed by Resting-State fMRI

Mild cognitive impairment (MCI) is considered to be the prodromal stage of Alzheimer's disease. The amygdala, which is considered to be a hub, has been shown to have widespread brain connections with many cortical regions. Longitudinal alterations in the functional connectivity of the amygdala remain unclear in MCI. We hypothesized that the impairment in the amygdala-cortical loop would be more severe in a follow-up MCI group than in a baseline MCI group and that these alterations would be related to the disease processes. To test this hypothesis, we used resting-state functional magnetic resonance imaging to investigate alterations in amygdalar connectivity patterns based on longitudinal data from 13 MCI subjects (8 males and 5 females). Compared to the baseline, decreases in functional connectivity were mainly found located between the amygdala and regions at the conjunction of the temporal-occipital system and the regions included in the default mode network in the follow-up MCI individuals. The alterations in the functional connectivity of the identified regions were validated in an independent dataset. Specifically, reduced amygdalar connectivity was significantly correlated with cognitive abilities. These findings indicate that impairments in the functional connectivity of the amygdala may be potential biomarkers of the progression of MCI.