Impaired Functional Connectivity of the Thalamus in Alzheimer's Disease and Mild Cognitive Impairment: A Resting-State fMRI Study

Objectives: The current study evaluated whether the functional connectivity pattern of the thalamo-cortical network in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) would show disease severity-related alterations. Methods: Resting-state functional magnetic resonance imaging (MRI) data were obtained from 35 patients with AD, 27 patients with MCI and 27 subjects with normal cognition (NC). First, the altered functional connectivity pattern in AD patients was evaluated in comparison to NC subjects. Second, the MCI subjects were included to evaluate how different stages of disease affect the functional connectivity pattern of the thalamus. Finally, a correlation analysis was performed between the strength of the functional connectivity of the identified regions and various clinical variables to evaluate the relationship between the strength of functional connectivity and the cognitive abilities of MCI and AD patients. Results: When compared to NC subjects, AD patients showed decreased functional connectivity between the left thalamus and brain regions including the precuneus/posterior cingulate cortex, right middle frontal gyrus and left inferior frontal gyrus. Decreased functional connectivity was also found between the right thalamus and right middle frontal gyrus and left inferior parietal lobule/angular gyrus. In addition, increased functional connectivity was observed between the bilateral thalamus and brain regions including the middle frontal gyrus, middle temporal gyrus, inferior temporal gyrus, superior parietal lobule, postcentral gyrus and precuneus. Functional connectivity between the bilateral thalamus and the identified brain regions of MCI subjects was intermediate in comparison to the functional connectivity of AD and NC subjects. A significant correlation between the fitted functional connectivity strength and the clinical variables was also detected. Conclusion: Our results revealed disease severity-related alterations of the thalamo-default mode network and thalamocortical connectivity in AD and MCI patients. These results support the hypothesis of network disconnection in AD.