Spatiotemporal profiling of functional network overlapping modules in Alzheimer's disease

Alzheimer's disease (AD) is characterized by progressive neural network degradation. In brain functional networks, overlapping module structures provide more accurate representations of brain function than nonoverlapping structures. Since the involvement of overlapping nodes in multiple modules can vary over time, investigating dynamic functional changes in the brain may provide deeper insights into the structural characteristics of these overlapping modules. However, the spatiotemporal dynamics of overlapping modular brain organization remain unclear. We employed resting-state fMRI to explore the overlapping modular organization and dynamic multilayer modules in 64 AD (Age_mean = 74.04) and 61 healthy controls (HC, Age_mean = 74.86) from the Alzheimer's Disease Neuroimaging Initiative. Compared with HC, AD exhibited increased overlapping modules and decreased modularity, with altered nodal overlapping probability, particularly in the superior frontal cortex and hippocampus. Higher nodal overlapping probability correlated with greater flexibility and was associated with larger amyloid deposits. Lasso regression analysis further revealed strong correlations between overlapping nodal characteristics and cognitive performance. Our findings suggest that overlapping nodes are critical components in AD, demonstrating high amyloid deposition, significant functional flexibility, and strong associations to cognitive behavior. These alterations may enhance the understanding of AD pathology and contribute to the development of biomarkers for improved diagnosis and therapeutic strategies.