The Impact of Sex Hormones and Aging on Sleep-Dependent Memory Formation

Age and sex are two of the three major risk factors for Alzheimer’s disease. Sex differences have been shown across a wide range of cognitive skills in young and older adults. In addition, the aging brain results in decreases in both Long-Term Memory (LTM) and Working Memory (WM). A growing body of evidence shows that sleep is critical for the formation of memories, with several electrophysiological events, including slow oscillations (SO 0.5-1Hz) and sleep spindles (12-15Hz), linked with memory consolidation. Sleep has been shown to be influenced by sex, sex hormones’ fluctuation and aging. Therefore, it is possible that sleeping brain processes memory differently among men and women and among older and younger adults. This dissertation investigates the role of both menstrual phase and aging on sleep related memory formation. In Chapter 1, I explore the role of sex differences and menstrual phase on sleep dependent LTM consolidation among younger adults. I find superior pre-nap memory performance on a verbal memory task in women compared with men. Among women, post-nap memory retention was modulated by menstrual phase, with women showing more forgetting following a nap in their perimenses phase (−5 days to +6 days from the start of menses) compared to their non-perimenses (outside of the perimenses phase). In addition, three profiles emerged between brain activity and performance. In men, performance was associated with the temporal coupling of spindles and slow oscillations (i.e., spindle/SO coincidence) as well as the number of spindles. During non-perimenses, women’s performance was related with SOs only, whereas performance during perimenses was associated with sleep spindles only. In Chapter 2, I explore the role of sleep, wake and quiet rest on WM training among older adults. I show that WM improved within a day of practice only after offline periods containing nap and quiet rest, but not wake, with similar sleep-dependent mechanisms as LTM consolidation (e.g., SOs and the coupling of sigma and SOs). Finally in Chapter 3, I investigate the role of WM on emotional LTM performance among younger and older adults. I find a superior memory performance for younger adults, a positivity memory bias among older adults, and a positive relation between WM and LTM only among younger adults. Together, the studies from this dissertation show evidence for a role of sex, sex hormones’ fluctuation, and aging, on sleep and memory. With the reported declines in sleep and memory emerging in older adulthood and menopausal women experiencing a sudden drop in sex hormones, this dissertation highlights the importance of possible interactions among biological factors, such as sex and aging, while studying sleep and memory with the goal of illuminating new paths towards the prevention of Alzheimer’s disease