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Sleep disturbances are commonly reported among patients with Alzheimer’s Disease (AD). Further, the disruption of subcortical areas such as the Basal Forebrain (BF) and its constituent Nucleus Basalis of Meynert (NBM), which play an important role in maintaining wakefulness or alertness (also known as vigilance), occurs early in AD. In this study, we delineate vigilance-linked fMRI patterns in an aging population and determine how these patterns relate to subcortical integrity and cognition. We used fMRI data from the Vanderbilt Memory and Aging Project dataset, consisting of 49 MCI patients and 75 healthy controls. Since external measures of vigilance are not present during fMRI, we used a data-driven technique for extracting vigilance information directly from fMRI data. With this approach, we derived subject-specific spatial maps reflecting a whole-brain activity pattern that is correlated with vigilance. We first assessed the relationships between cognitive measures (subject memory composite and executive function scores) and structural measures (BF and NBM volumes obtained from subject-specific segmentation methods) using Pearson correlations. BF and NBM volumes were found to be significantly correlated with memory composite in MCI subjects and with executive function in HCs. We then performed a mediation analysis to evaluate how NBM volume may mediate fMRI-derived vigilance effects on memory composite scores in MCI subjects. fMRI vigilance activity and memory composite were significantly associated in the hippocampus, posterior cingulate cortex, and anterior cingulate cortex, regions involved in the default-mode and salience networks. These results suggest that cognitive decline in AD may be linked with both subcortical structural changes and vigilance-related fMRI signals, opening new directions for potential functional biomarkers in pathological aging populations.
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