BackgroundAlzheimer’s Disease (AD) is the most common form of dementia. Its early stage, amnestic Mild Cognitive Impairment (aMCI), is characterized by disrupted information flow in the brain. Previous studies have yielded inconsistent results when using electrophysiological techniques to investigate functional connectivity changes in AD, and a contributing factor may be the study of brain activity divided into frequencies.MethodsOur study aimed to address this issue by employing a cross-frequency approach to compare the functional networks of 172 healthy subjects and 105 aMCI patients. Using magnetoencephalography, we constructed source-based multilayer graphs considering both intra- and inter-frequency functional connectivity. We then assessed changes in network organization through three centrality measures, and combined them into a unified centrality score to provide a comprehensive assessment of centrality disruption in aMCI.ResultsThe results revealed a noteworthy shift in centrality distribution in aMCI patients, both in terms of spatial distribution and frequency. Posterior brain regions decrease synchrony between their high-frequency oscillations and other regions’ activity across all frequencies, while anterior regions increase synchrony between their low-frequency oscillations and other regions’ activity across all frequencies. Thus, posterior regions reduce their relative importance in favor of anterior regions.ConclusionsOur findings provide valuable insights into the intricate changes that occur in functional brain networks during the early stages of AD, demonstrating that considering the interplays between different frequency bands enhances our understanding of AD network dynamics and setting a precedent for the study of functional networks using a multilayer approach.