Progressive Changes in Hippocampal Resting-state Connectivity Across Cognitive Impairment A Cross-sectional Study From Normal to Alzheimer Disease

We investigate the changes in functional connectivity of the left and right hippocampus by comparing the resting-state low-frequency fluctuations in the blood oxygen level-dependent signal from these regions with relation to Alzheimer disease (AD) progression. AD patients were divided into subgroups based on the clinical dementia rating (CDR) scores. Patients with amnestic mild cognitive impairment (aMCI) were also analyzed as an intermediate stage between normal controls and AD. We found that the total functional connectivity of both the right and left hippocampus was maintained during aMCI and the early stages of AD and that it decreased in the later stages of AD. However, when total functional connectivity was broken down into specific regions of the brain, we observed increased or decreased connectivity to specific regions beginning with aMCI. Direct correlation analysis in seeding the left hippocampus revealed a significant decrease in the functional connectivity with the posterior cingulate cortex region and lateral parietal areas, and an increase in functional connectivity in and the anterior cingulate cortex beginning with aMCI. In this study, we were able to quantify the deterioration of resting-state hippocampal connectivity with disease severity and formation of compensatory recruitment in the early stages of AD.