Cerebrospinal fluid Aβ42 moderates the relationship between brain functional network dynamics and cognitive intraindividual variability.

As Alzheimer's disease (AD) pathology accumulates, resting-state functional connectivity (rs-fc) within and between brain networks decreases, and fluctuations in cognitive performance known as intraindividual variability (IIV) increase. Here, we assessed the relationship between IIV and anticorrelations 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 anticorrelations between DMN × DAN were higher in individuals with AD compared with cognitively normal participants. As DMN × DAN relationship became more positive, cognitive IIV increased, indicating that stronger anticorrelations 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 DMN × DAN, 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 the early stages of AD.