Biological sex and bilingualism: Its impact on risk and resilience for dementia

INTRODUCTION: The relationship between biological sex, considered a risk factor for Alzheimer's disease (AD), and bilingualism, a resilience factor, is unclear. We assessed this relationship in 335 individuals with mild cognitive impairment (MCI) in a Canadian cohort. METHODS: We used univariate analysis and structural equation modelling to study the relationship between female sex and bilingualism. We created a resilience index (RI) for each participant using the residual approach. Logistic and linear regressions predicted cognitive and brain health in relation to RI. RESULTS: Overall, bilingual males had increased RI. Higher RI was associated with less risk of AD and less neuropathology and glial activation as indexed by plasma p-tau181, neurofilament light, and glial fibrillary acidic protein. DISCUSSION: In MCI, the combination of elevated estradiol levels due to aromatization and bilingualism may provide synergistic protection for verbal memory, making old bilingual males more resilient. Highlights: Sex steroids influence verbal memoryIn a structural equation modeling (SEM) model, verbal memory mediates cognitive declineElevated estradiol from aromatization makes old bilinguals more resilient.