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

Alzheimer's disease (AD) represents a major challenge in neurodegenerative disease research, 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 controls, subjective cognitive decline (SCD), and mild cognitive impairment (MCI) groups. Amplitude Envelope Correlation with leakage correction was calculated over MEG signals with a sliding window, and the correlation across trials 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 progress along the AD continuum. Notably, the frontal and temporal lobes and regions within the default mode network exhibited pronounced dFC reductions. Finally, this dFC decline significantly correlated with cognitive performance deterioration and structural brain changes, 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 spectrum of AD, 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. ### Competing Interest Statement The authors have declared no competing interest.