Age and Sex-Related Effects on Single-Subject Gray Matter Networks in Healthy Participants

Recent developments in image analysis have enabled an individual's brain network to be evaluated and brain age to be predicted from gray matter images. Our study aimed to investigate the effects of age and sex on single-subject gray matter networks using a large sample of healthy participants. We recruited 812 healthy individuals (59.3 ± 14.0 years, 407 females, and 405 males) who underwent three-dimensional T1-weighted magnetic resonance imaging. Similarity-based gray matter networks were constructed, and the following network properties were calculated: normalized clustering, normalized path length, and small-world coefficients. The predicted brain age was computed using a support-vector regression model. We evaluated the network alterations related to age and sex. Additionally, we examined the correlations between the network properties and predicted brain age and compared them with the correlations between the network properties and chronological age. The brain network retained efficient small-world properties regardless of age; however, reduced small-world properties were observed with advancing age. Although women exhibited higher network properties than men and similar age-related network declines as men in the subjects aged < 70 years, faster age-related network declines were observed in women, leading to no differences in sex among the participants aged ≥ 70 years. Brain age correlated well with network properties compared to chronological age in participants aged ≥ 70 years. Although the brain network retained small-world properties, it moved towards randomized networks with aging. Faster age-related network disruptions in women were observed than in men among the elderly. Our findings provide new insights into network alterations underlying aging.