Sex differences emerge after the menopause transition:Females show accelerated decline in episodic memory for spatial context at midlife

Background and ObjectivesThe ability to remember past events in rich contextual detail (episodic memory) declines with advancing age, with accelerated decline around midlife. Past research indicates there may be sex differences in cognitive aging trajectories and risk for age-related neurodegenerative diseases, i.e. Alzheimers Disease. Yet, little is known about how biological sex affects episodic memory in the adult lifespan. We examined age differences in episodic memory for spatial context in males and females. Research Design and Methods192 adults aged 21 to 65 (M=44, SD=13, 134 females) completed a face-location task measuring spatial context memory (correct spatial context retrieval rates) and facial item memory (correct recognition rates), and the California Verbal Learning Test version II (CVLT-II) measuring verbal item memory (long free recall, cued recall, and recognition rates). Changepoint regression analysis was used to estimate the slope of memory across age and any significant shifts in the slope (indicating critical transition periods). ResultsRegression analyses revealed that the best-fitting model for females on spatial context memory accuracy was a one-changepoint model, with gradual decline of 2% (SE=1) fewer correct responses per year of age from age 21 until age 50 (95% CI 41, 58), shifting to more rapid decline of 4% (SE=1) fewer correct responses per year of age until age 65. The best fitting model for males on spatial context memory accuracy was linear, with no significant changes across ages. The best fitting models for both sexes were linear for facial item memory accuracy, spatial context memory and facial item memory reaction times, and verbal item memory accuracy. Discussion and ImplicationMales and females show similar decline on spatial context memory from young adulthood until midlife, after which females show greater decline than males. Importantly, disaggregating by sex indicated that past midlife effects on episodic memory for context may be driven by a specific group of females (post-menopausal), as accelerated decline occurred at the same time as menopause in midlife females and did not occur in midlife males. Translational SignificanceO_ST_ABSProblem AddressedC_ST_ABSWe use changepoint regression to examine how biological sex influences age differences in remembering the context of past events (episodic memory). Main outcomeFemales, but not males, showed significantly greater decline on spatial context memory (i.e., correctly recalling the location of previously learned information) after age 50, which aligns with the time of menopause in midlife females. Implications for TranslationEpisodic memory for spatial context shows accelerated decline in females after midlife compared to before midlife, but not in midlife males, indicating the potential influence of menopause on aging of memory.