Dynamics of brain connectivity across the Alzheimer’s disease spectrum through magnetoencephalography

Changes in static functional connectivity have been extensively linked to Alzheimer's Disease (AD), however, dynamic functional connectivity (dFC) across the AD continuum remains understudied. The current investigation leverages the high temporal resolution of MEG to dissect the dynamics of brain connectivity alterations across various stages of AD and their association with cognitive decline and structural brain changes. 321 participants were included, categorized into healthy control, subjective cognitive decline (SCD), and mild cognitive impairment (MCI) groups. Amplitude envelope correlation with leakage correction was calculated over MEG signals using a sliding window, and the correlation across epochs was studied to assess dFC. We explored dFC associations with cognitive scores, grey matter volume, and white matter fractal anisotropy. Whole-brain dFC declined along the AD continuum, especially in the alpha and beta bands, with pronounced reductions in the frontal and temporal lobes and default mode network regions. Moreover, these dFC changes correlated with cognitive decline and structural brain alterations. The present study underscores the relevance of dFC in capturing early temporal dynamic alterations, linking high-frequency activity in association cortices to white matter integrity and cognitive deterioration, thus highlighting the metric's potential as a sensitive marker of disease progression.