Sex differences in patterns of associative memory-related activation in individuals at risk of Alzheimer's disease

The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how re-lationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Iden-tification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in under-standing the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.(c) 2022 Elsevier Inc. All rights reserved.