Scientific Rationale:
Our preliminary animal studies demonstrate that ovarian hormone deprivation causes early white matter microstructural alterations and cognitive deficits. However, it remains unclear how these findings translate to humans and how sleep disturbances, common during perimenopause, interact with hormonal changes. This project utilizes UK Biobank data to bridge the gap between basic science and epidemiology.
Research Questions:
1. Is sleep disturbance an independent risk factor for white matter injury and cognitive decline, distinct from vasomotor symptoms?
2. What genetic determinants (via GWAS) explain susceptibility to sleep-related brain aging during the menopausal transition?
3. Can lifestyle factors (e.g., physical activity) mitigate the neurocognitive impact of menopause?
Objectives:
Using multimodal MRI (DTI, fMRI, T2-FLAIR), genetic, and cognitive data, we aim to:
1. Validate animal findings by characterising white matter integrity in early post-menopausal women in relation to hormone profiles.
2. Investigate the impact of sleep quality on white matter hyperintensities and cognitive function in perimenopausal women.
3. Determine if sleep acts as a modifiable mediator between hormonal changes and neurocognitive health.
Public Interest:
This research aims to identify specific windows for early intervention (such as sleep management) to preserve brain health in women, potentially reducing the future burden of neurodegenerative diseases.
