Biological Sex and Menopause Status Affect Neural Correlates of Episodic memory in Midlife and Older Age

Age-related episodic memory decline can be an early sign of Alzheimer’s disease (AD) – a disease that is more prevalent in females than males. Importantly, there is growing evidence that midlife is a critical period in adulthood when episodic memory declines, and changes in brain regions affected by AD arise. Midlife is also the time that females with ovaries experience spontaneous menopause. Yet, little is known about the effects of biological sex and menopause status on age-related episodic memory decline and its neural correlates at midlife. In this talk I will present results from the ongoing Brain Health at Midlife and Menopause (BHAMM) study which aims to fill this knowledge gap and determine what factors support and/or hinder memory and brain function in males and females at midlife. Our initial results suggest that middle-aged females, but not males, exhibited age-related episodic memory decline, and that this effect was driven by post-menopausal females. Task-based fMRI analysis showed that memory decline at post-menopause was associated with altered activity in occipital, parahippocampal, lateral frontal, and parietal cortices, compared to premenopausal females. However, there was significant inter-individual variability in brain and memory function in post-menopause. Females with poor vascular health exhibited greater memory-related deficits in post-menopause. Together these studies highlight the importance of considering biological sex and menopause status in cognitive neurosciences.