Sex and menopause status alter age associations with spatial context memory and white matter microstructure at midlife

Poster Session F - Tuesday, April 16, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Rikki Lissaman^1,2,3 (rikki.lissaman@gmail.com), Sricharana Rajagopal^2,3, Julia Kearley^1,2, Stamatoula Pasvanis^2,3, Maria Natasha Rajah^1,2,3; ¹McGill University, ²Douglas Research Centre, ³Toronto Metropolitan University

Age-related decline in spatial context memory emerges in midlife, the time at which most females with ovaries transition from pre- to post-menopause. Recent evidence suggests that, in post-but not pre-menopausal females, advanced age is associated with lower occipito-temporal/parahippocampal activity and lower spatial context memory. However, it is currently unknown whether similar menopause effects are evident for brain structural connectivity and, in addition, whether such effects on the brain and cognition contribute to sex differences at midlife. To address this, we conducted a study on 96 cognitively unimpaired middle-aged adults (30 males, 32 pre-menopausal females, 34 post-menopausal females). Spatial context memory was assessed using an associative (face-location) memory paradigm, which included easy and hard variants, while white matter microstructure (fractional anisotropy [FA], mean diffusivity [MD]) was assessed using diffusion tensor imaging. Behaviorally, we found that females showed lower levels of spatial context memory with advanced age, independent of task difficulty. The detrimental effect of age was subsequently shown to be specific to post-menopausal females. At the neural level, multivariate partial least squares analyses revealed that advanced age was associated with lower FA and higher MD in predominantly frontal white matter tracts (e.g., anterior corona radiata, genu of corpus callosum), independent of sex and menopause status. However, the expression of this pattern was subsequently shown to be related to spatial context memory in females and post-menopausal females in particular. Overall, our results are consistent with the notion that the transition from pre- to post-menopause is a critical period in female brain aging.

Topic Area: LONG-TERM MEMORY: Development & aging