The intricate relationships between menopause, cardiometabolic risk factors, and brain health in women represent a critical yet understudied area of neuroscience. This thesis utilises neuroimaging, genetic, and biomedical data from large population-based datasets to identify risk factors contributing to white matter hyperintensities (WMHs) and other structural brain outcomes in healthy women, aiming to gain insights into factors driving women's postmenopausal brain health.
Using Bayesian linear models, Study I (n=10,251) demonstrated that a shorter reproductive span and higher abdominal adiposity were associated with higher WMH volume and older brain age in postmenopausal women, with potential synergistic effects. Study II (n=9,882) employed regression analyses to show that postmenopausal women had higher levels of several cardiometabolic risk factors compared to premenopausal women, and these markers were associated with higher WMH volume nearly a decade later. Study III used a drug-target Mendelian Randomisation approach to estimate causal effects of oestrogen receptor perturbation on brain outcomes, finding no significant associations with WMH volume, total grey matter volume, hippocampal volume, or Alzheimer's disease risk.
These findings indicate that both reproductive factors and cardiometabolic health could play important roles in women's brain health across menopausal years, and underscore the importance of maintaining cardiometabolic health throughout the menopausal transition to support healthier brain ageing. However, modest effect sizes and lack of conclusive causal evidence highlight the need for careful interpretation of clinical implications. Future research would benefit from longitudinal designs, diverse populations, and comprehensive assessments of female-specific factors to better inform targeted interventions for healthy body and brain ageing across menopausal years and beyond.