LAUSR

BACKGROUND Aging is accompanied by a gradual deterioration in multiple cognitive abilities and brain structures. Both cognitive function and white matter (WM) structure are found to be associated with neurodegeneration diseases and correlated with sex during aging. However, it is still unclear whether the brain structural change could be attributable to sex, and how sex would affect cognitive performances during aging. METHOD Diffusion MRI scans were performed on 1127 healthy participants (age range: 21 to 89) at a single site. The age trajectories of the WM tracts microstructure were delineated to estimate the turning age and changing rate between sexes. The canonical correlation analysis and moderated mediation analysis were used to examine the relationship between sex-linked WM tracts and cognitive performances. RESULTS The axon intactness and demyelination of sex-linked tracts during aging were multifaceted. Sex-linked tracts in females peak around 5 years later than those in males but change significantly faster after the turning age. Projection and association tracts (e.g., corticospinal tracts and parahippocampal cingulum) contributed to a significant decrease in visuospatial and executive functions. We discovered that there is a stronger indirect effect of sex-linked tracts on cognitive functions in females than in males. CONCLUSION Our findings suggest that the vulnerable projection and association tracts in females may induce negative impacts on integrating multiple functions, which results in a faster decrease in visuospatial and executive functions.