Grant: CIHR Strategic Master's Award - Sex and Gender in Health Research

Alzheimer's disease (AD) is the most common form of dementia in Canada. Female individuals comprise two-thirds of cases. AD is characterized by a progressive decline in memory for personal information and experiences (i.e. episodic memory). Midlife (ages 40 to 65) is a critical period for AD prevention due to the emergence of the earliest signs of AD at this stage. It is also at this time that females with ovaries experience menopause. Reproductive hormones such as estrogen, which have protective effects on the brain, are reduced following menopause. The changes experienced at menopause are associated with an increased risk for AD, but it is unclear why this risk varies across females. One possible explanation is that the presence of vascular risk factors (VRF) interacts with menopause status to influence AD risk. Vascular brain health can be assessed with the presence of white matter hyper-intensities (WMH), which act as substitute markers of vascular health given that they represent damages to the white matter. WMH are associated with a decline in episodic memory performance. Middle-aged (MA) post-menopause females have greater WMH burden in comparison to MA males and MA pre-menopause females. Previous studies show that there is an association between the presence of vascular risk factors, menopause, and episodic memory decline at midlife. However, this has not been explored in the context of WMH, which are highly relevant as they provide an insight into vascular brain health. In this study, we will use data from the ongoing Brain Health at Midlife and Menopause study to investigate the influence of age, biological sex, and menopause status on the association between WMH volumes and episodic memory at midlife. The influence of the APOE4 genotype, an established risk factor for AD, on the interactions described above will also be explored. Overall, this study will help AD prevention and management efforts and improve knowledge on women's brain health.