Differential predictability of cognitive profiles from brain structure in older males and females

Structural brain imaging parameters may successfully predict cognitive performance in neurodegenerative diseases but mostly fail to predict cognitive abilities in healthy older adults. One important aspect contributing to this might be sex differences. Behaviorally, older males and females have been found to differ in terms of cognitive profiles, which cannot be captured by examining them as one homogenous group. In the current study, we examined whether the prediction of cognitive performance from brain structure, i.e. region-wise grey matter volume (GMV), would benefit from the investigation of sex-specific cognitive profiles in a large sample of older adults (1000BRAINS; N = 634; age range 55-85 years). Prediction performance was assessed using a machine learning (ML) approach. Targets represented a) a whole-sample cognitive component solution extracted from males and females, and b) sex-specific cognitive components. Results revealed a generally low predictability of cognitive profiles from region-wise GMV. In males, low predictability was observed across both, the whole sample as well as sex-specific cognitive components. In females, however, predictability differences across sex-specific cognitive components were observed, i.e. visual working memory (WM) and executive functions showed higher predictability than fluency and verbal WM. Hence, results accentuated that addressing sex-specific cognitive profiles allowed a more fine-grained investigation of predictability differences, which may not be observable in the prediction of the whole-sample solution. The current findings not only emphasize the need to further investigate the predictive power of each cognitive component, but they also emphasize the importance of sex-specific analyses in older adults.