Whole-Brain Dynamics Disruptions in the Progression of Alzheimer's Disease: Understanding the Influence of Amyloid-Beta and Tau

INTRODUCTION: Alzheimer's disease (AD) affects brain structure and function along its evolution, but brain network dynamic changes remain largely unknown. METHODS: To understand how AD shapes brain activity, we investigated the spatiotemporal dynamics and resting state functional networks using the intrinsic ignition framework, which characterizes how an area transmits neuronal activity to others, resulting in different degrees of integration. Healthy participants, MCI, and AD patients were scanned using resting state fMRI. Mixed effects models were used to assess the impact of ABeta and tau, at the regional and whole-brain levels. RESULTS: Dynamic complexity is progressively reduced, with Healthy participants showing higher metastability (i.e., a more complex dynamical regime over time) than observed in the other stages, while AD subjects showed the lowest. DISCUSSION: Our study provides further insight into how AD modulates brain network dynamics along its evolution, progressively disrupting the whole-brain and resting state network dynamics.