Abstract
Mild cognitive impairment (MCI) of the amnestic type is considered to be a transitionary stage between healthy aging and Alzheimer's disease (AD). Previous studies have demonstrated that intrinsic functional connectivity of the default network (DN) is altered in normal aging and AD and impacts both within- and between-network connectivity. Although changes within the DN have been reported in MCI, it remains uncertain how interactions with other large-scale brain networks are altered in this prodromal stage of AD. We investigated within- and between-network connectivity in healthy older adults (HOAs) and older adults with MCI across 3 canonical brain networks: DN, dorsal attention network, and frontoparietal control network. We also assessed how patterns of functional connectivity among the 3 networks predicted cognitive status and age using multivariate partial least squares. A total of 91 MCI and 71 HOA resting-state scans were analyzed from the Alzheimer's Disease Neuroimaging Initiative. There were 3 key findings. First, a circumscribed pattern of greater between-network and interhemispheric connectivity was associated with higher cognitive status in HOAs. Second, for individuals with MCI, cognitive status was positively associated with a more distributed, less-differentiated pattern of intrinsic functional connectivity across the 3 networks. Finally, greater within-network functional connectivity was positively associated with cognitive status for HOAs irrespective of age; however, this compensation-like effect diminished with increasing age for participants with MCI. Although reliable differences between healthy aging and MCI in the intrinsic network architecture of the brain are apparent, these differences emerge as shifting associations between network interactivity, cognitive functioning, and age.