High brain network system segregation is differentially linked with cognitive performance across the life span.

Healthy aging is marked by changes in both cognitive performance and the organization of brain networks. Declines in cognition have been linked to reductions in system segregation (SS), as older adults typically exhibit less segregated functional networks than younger adults. While lower segregation has been associated with diminished cognitive abilities, it remains unclear how individual variability in SS contributes to cognitive outcomes across the lifespan. Here, we examine relationships between SS and three cognitive domains (semantic, executive, episodic memory) using resting-state fMRI data from 179 younger (18-29 years) and 117 older adults (60-89 years). SS was measured globally and for specific networks using Schaefer's 7-network parcellation. Our findings confirmed a global age-related reduction in SS, particularly impacting the somatomotor, ventral attention, and frontoparietal networks. This reduction in global SS mediated negative effects of age group on semantic and executive performance. When examining younger and older groups separately, we found that higher SS was associated with better semantic performance in both groups, while observing a similar positive association with executive performance only in older adults, suggesting that executive function becomes increasingly dependent on preserved network architecture with age. Maintaining SS may therefore be critical for supporting healthy cognitive aging.