Sex difference in brain reserve of working memory among older adults

Working memory is one of the core cognitive functions that declines in older adulthood. Brain reserve (BR) refers to neurobiological status of the brain that supports cognition, offering a valuable neurostructural framework for understanding working memory decline among older adults. However, most existing studies rely on gross, whole-brain measures of BR which may lack sensitivity to specific cognitive functions, and few studies have examined their sex differences. Based on 131 healthy older adults (aged 52-86) from Australia, this study used multimodal imaging data, including grey matter volume, cortical thickness, and white matter tract integrity, to identify BR proxies for older adults' working memory, and to test for sex differences and their interaction effects with age. Results indicate that BR proxies for older adults' working memory were primarily concentrated in white matter tracts related to sensory processing and hemispheric integration, including the acoustic, optic, and thalamic radiations, as well as the corpus callosum, while whole-brain BR proxies showed no significant correlations with working memory performance. Meanwhile, BR proxies significantly mediated the negative correlation between age and working memory performance. No sex differences were observed in behavioral measures of working memory; however, women exhibited higher structural integrity and smaller age-related differences in multiple critical white matter pathways compared to men during late adulthood. These findings suggest that older women have better preserved working memory-related BR, supporting the theory that BR acts as "neurobiological capital" to buffer supposed age-related cognitive decline. Our study provides new empirical evidence for understanding sex differences in BR, which shows a female advantage in later life, as well as the protective mechanisms during working memory aging.