Cerebellar Topological Alterations Across the Alzheimer’s Disease Continuum

Abstract

Background: Alzheimer’s disease (AD) is characterized as a network disconnection syndrome. Despite evidence implicating the cerebellum in cognitive network integration, its associated electrophysiological network topology dynamics across the AD continuum remain unexplored.Methods: We enrolled 34 healthy controls (HC), 40 patients with mild cognitive impairment (MCI), and 30 AD patients in this study. Cortical and cerebellar signals were recorded with a whole-brain EEG cap, and weighted functional connectivity networks were constructed using the phase-locking value (PLV). Graph theory was used to analyze network topological metrics across the AD continuum, focusing on cerebellar nodes. Topological metrics were correlated with neuropsychological scores, and networkbased statistics (NBS) identified differential connectivity patterns among groups.Results: Network changes were most prominent in the theta band, with additional alterations in the delta band. Both MCI and AD groups showed reduced small-world metrics, although small-world organization remained present. These groups also showed increased nodal centrality in the frontal, occipital and cerebellar regions (at CB1, CB2 and CBZ in MCI but only at CBZ in AD) but decreased in the central and temporal regions. NBS analysis identified selective theta-band reorganization of cerebellocortical connectivity. An inverted U-shaped relationship was found between cerebellar nodal centrality and neuropsychological scale scores.Conclusions: The cerebellar theta rhythm may be a key pattern involved in cognitive processing, and the topological changes of the cortical-cerebellar network may represent candidate electrophysiological network markers across different AD stages. These markers may reflect stage-related differences in cerebellar function, shifting from compensation in MCI to decompensation in AD.