Age-related Changes in Brain Connectivity: Cross-sectional and Longitudinal Effects

Abstract

Age-related changes in functional connectivity within and between brain networks may contribute to cognitive and behavioral decline in aging. Prior research has consistently reported declines in within-network connectivity with age, though findings on between-network connectivity change have been mixed. Most studies have relied on cross-sectional designs, making it difficult to disentangle age-related effects from confounding cohort effects. Therefore, this study utilizes both cross-sectional (between-subject) and longitudinal (within-subject) data sets and employs mixed-effects models to elucidate age-related changes in resting-state functional connectivity across eight large-scale brain networks. After clinical screening and motion-based quality control, analyses were based on resting-state fMRI from 53 younger adults and 127 older adults, 45 of whom were rescanned approximately four years later. We examined whole-brain within-network connectivity, between-network connectivity, and network segregation. Cross-sectionally, older age was associated with lower within-network (p < 0.001) and between-network connectivity (p = 0.003), whereas segregation showed a more modest cross-sectional reduction that was concentrated in the salience and visual networks. Longitudinally, over approximately four years both within-network (p = 0.003) and between-network (p = 0.003) connectivity declined, while segregation did not change (p = 0.546). Declines in within- and between-network connectivity were broad rather than network-specific, with the Default Mode and Salience networks most consistently affected.