CSF Aβ42 Moderates the Relationship Between Brain Functional Network Dynamics and Cognitive Intra-Individual Variability

Abstract As Alzheimer Disease (AD) pathology accumulates, resting state functional connectivity (rs-fc) within and between brain networks decreases, and fluctuations in cognitive performance known as intra-individual variability (IIV) increase. Here we assessed relationship between IIV and anti-correlations in rs-fc between the default mode network (DMN)-dorsal attention network (DAN) in cognitively normal older adults and symptomatic AD participants. We also evaluated the relationship between cerebrospinal fluid (CSF) biomarkers of AD (amyloid beta [Aβ42] and tau) and IIV-anticorrelation in rs-fc. We observed that cognitive IIV and anti-correlations between DMNxDAN were higher in individuals with AD compared to cognitively normal participants. As DMNxDAN relationship became more positive, cognitive IIV increased, indicating that stronger anti-correlations between networks support more consistent cognitive performance. Moderation analyses indicated that continuous CSF Aβ42, but not CSF total tau, moderated the relationship between cognitive IIV and DMNxDAN, collectively demonstrating that greater amyloid burden and alterations in functional network dynamics are associated with cognitive changes seen in AD. These findings are valuable, as they suggest that amyloid affects cognitive functioning during early stages of AD.