Grant: Proect Grant - PA: Intersectionality in Sex, Gender and Health Research

Episodic memory decline is a hallmark of aging and can be an early sign of Alzheimer's disease (AD). However, there is significant variability in how age affects memory and related brain structures and their function. There is growing evidence that biological sex may contribute to the observed variability in memory and brain aging, and that female biological sex may increase one's risk for AD. This highlights the need to study how biological sex affects memory and related brain function in aging. We have found evidence of sex differences in the neural basis of age-related episodic memory decline. We also found that midlife is a critical age when age-related episodic memory decline emerges. Midlife is the time most females menopause. Importantly, some females experience episodic memory deficits and show differences in memory-related brain functions during menopause. Therefore, how a female experiences menopause may place some females at greater risk for late life cognitive decline and AD. This highlights the need to understand what factors contribute to poorer memory and brain function in middle-aged (MA) males and MA Pre-, Peri- and Post-menopausal (Meno) females. To this aim we will conduct a large cohort structural and functional MRI study in which MA are scanned while performing episodic memory tasks. We will use multivariate brain imaging analyses to test the following hypotheses: 1) Post-Meno MA females will perform poorer than other MA groups on the memory task, 2) Poorer memory performance will correlate with: i) smaller posterior HC and HC subfield volumes, and ii) altered activity and connectivity in the posterior HC episodic memory network. Our results will advance our knowledge of how biological sex and menopause status affects brain health and memory function in a cognitively unimpaired sample of MA.