Linking White Matter Integrity to Recognition Memory Speed: Fixel-Based and Fornix Analyses in Young to Middle Adulthood

Abstract

Age-related differences in white matter structure are increasingly understood as nonlinear, regionally specific, and behaviorally relevant. Using whole-brain fixel-based analysis (FBA), we examined how recognition memory speed relates to micro- and macrostructural white matter properties across a sample spanning young to middle adulthood. Slower response times were associated with higher fiber density (FD) in left frontoparietal tracts, nonlinear increases in fiber cross-section (log(FC)) in the anterior corpus callosum, and elevated combined fiber density and cross-section (FDC) in posterior callosal and cingulum pathways. These associations were most pronounced among individuals in the later decades of this age range, suggesting that white matter morphology reflects both extended maturation and emerging age-related decline. In a separate, hypothesis-driven analysis, we applied deterministic tractography to reconstruct the fornix and extracted mean fractional anisotropy (FA) along its length. Greater fornix FA and younger age together explained 34% of the variance in retrieval speed. These findings highlight regionally distinct structural contributions to memory performance and support lifespan models emphasizing individual variability and neuroplasticity in white matter development. This integrative approach underscores the value of combining whole-brain and tract-specific analyses to advance our understanding of white matter contributions to cognitive aging. HighlightsO_LISlower RT linked to higher fiber density in left frontoparietal white matter C_LIO_LISlower RT associated with nonlinear increases in anterior corpus callosum log(FC) C_LIO_LIFDC increased in posterior callosal and cingulum tracts in slower older adults C_LIO_LIFindings support prolonged maturation and regionally specific age-related decline C_LIO_LIFornix FA and age explained 34% of variance in memory retrieval speed C_LI