Dynamics of Brain Connectivity across the Alzheimer's Disease Spectrum: a magnetoencephalography study

Alzheimers disease (AD) represents a major challenge in neurodegenerative disease research, as it is characterized by a complex pathophysiology that involves not only structural but also functional changes in the brain. While changes in static functional connectivity have already been linked to AD, there is still a lack of research studying dynamic functional connectivity (dFC) across the AD continuum, which could be crucial for identifying potential biomarkers for early diagnosis and tracking disease progression. This study 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 in this study, 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 at whole-brain and node level. Finally, we explored dFC associations with cognitive scores, grey matter volume, and white matter fractal anisotropy. The study unveils a significant reduction in whole-brain dFC, especially within the alpha and beta frequency bands, as individuals advance along the AD continuum. Notably, the frontal and temporal lobes, as well as regions within the default mode network, exhibited pronounced dFC reductions. Finally, dFC significantly correlated with cognitive performance and changes in structural brain, suggesting the potential of the proposed dFC metric as sensitive indicator for monitoring disease progression. This investigation provides crucial insights into the temporal dynamics of brain connectivity alterations in the early stages of the AD spectrum, underlining the importance of dFC changes as reflective of cognitive and anatomical degeneration. The findings hint towards a strong relationship between connectivity profiles and white matter integrity, especially for high frequency activity in the association cortices. Key PointsO_LIDynamic functional connectivity declines over the AD spectrum. C_LIO_LIDynamic functional connectivity reductions are most prominent in orbitofrontal, temporal, and DMN-related areas. C_LIO_LICognitive performance, brain volumetrics, and white matter integrity parameters positively correlate with dynamic functional connectivity over the whole AD spectrum, and most significantly among mild cognitive impairment participants. C_LI