Female sex is a biological risk factor for the development of late-onset Alzheimer’s Disease (AD), reflected by a greater lifetime risk and greater neural pathological markers. Two proposed female-specific risk factors that may contribute to elevated AD risk are reduced lifetime exposure to endogenous ovarian hormones, for example as a result of the menopausal transition, and increased X-linked gene expression. However, the role of genotypic sex remains understudied compared to studies addressing that of phenotypic sex. An additional modifiable risk factor for AD is the occurrence of sleep disturbances, reported by 40-60% of postmenopausal women. Sleep is important in maintaining brain health, while disruption may contribute to the development of AD and peripheral inflammation. However, the combined contribution of sleep disturbances and hormonal/chromosomal sex on peripheral inflammation and AD risk remains unexplored. The aim of our proposed study is to understand whether midlife-specific changes in hormonal milieu and/or chromosomal sex could act as modulators on sleep-loss specific effects on inflammation, and potentially increased risk of cognitive decline and AD-related pathology. We will use the following data:
Demographic data: To identify and categorize participants.
Sleep-wake data: To assess sleep quality and identify sleep disturbances.
Structural and functional MRI scans data: To identify differences in key brain area structures.
Cognitive assessments: To identify cognitive ability on domains sensitive to menopause and sleep.
Biomarker data: To assess markers indicative of AD pathology.
Genetic data: To run a GWAS on X-/Y-linked genes to identify SNPs.
We will investigate by exploring sex differences in cognitive performance, structural and functional connectivity and inflammatory markers of sleep disturbed postmenopausal individuals and age-matched male controls.
