No sex differences in the association between regional brain structure abnormalities and cognitive functioning in a geriatric memory clinic population

Aging Brain. 2025 May 4;7:100137. doi: 10.1016/j.nbas.2025.100137. eCollection 2025.

ABSTRACT

Differences between men and women in cognitive impairment and neurodegeneration are not yet well understood. Although sex differences in brain structure abnormalities, including white matter hyperintensities (WMH) and grey matter (GM) atrophy, have been associated with cognitive decline in the ageing population, the evidence is limited and inconclusive. Therefore, we explored sex differences in brain structure abnormalities and in the association between brain structure abnormalities and cognitive functioning. We analyzed global and regional volumetric measures of WMH and GM of 475 patients visiting an academic geriatric memory clinic in the Netherlands with multiple linear regression analyses. For both global and regional WMH and GM, we found no sex differences in brain structure abnormalities. We also found no interaction of sex on the association between brain structure abnormalities and cognitive functioning. We reflect on using a binary classification of men and women based on sex in this study, which might overlook individual differences and does not elucidate gender-related factors that influence health and risk of pathology. Future studies should focus on exploring the relationship between sex and gender on brain structure and cognitive functioning beyond this binary model, by including more data on social context, more diverse populations and using intersectional approaches.

PMID:40421403 | PMC:PMC12104656 | DOI:10.1016/j.nbas.2025.100137