Impact of sex steroids and reproductive stage on sleep-dependent memory consolidation in women

Abstract

Age and sex are two of the three major risk factors for Alzheimer's disease (ApoE-e4 allele is the third), with women having a twofold greater risk for Alzheimer's disease after the age of 75 years. Sex differences have been shown across a wide range of cognitive skills in young and older adults, and evidence supports a role for sex steroids, especially estradiol, in protecting against the development of cognitive decline in women. Sleep may also be a protective factor against age-related cognitive decline, since specific electrophysiological sleep events (e.g. sleep spindle/slow oscillation coupling) are critical for offline memory consolidation. Furthermore, studies in young women have shown fluctuations in sleep events and sleep-dependent memory consolidation during different phases of the menstrual cycle that are associated with the levels of sex steroids. An under-appreciated possibility is that there may be an important interaction between these two protective factors (sex steroids and sleep) that may play a role in daily fluctuations in cognitive processing, in particular memory, across a woman's lifespan. Here, we summarize the current knowledge of sex steroid-dependent influences on sleep and cognition across the lifespan in women, with special emphasis on sleep-dependent memory processing. We further indicate gaps in knowledge that require further experimental examination in order to fully appreciate the complex and changing landscape of sex steroids and cognition. Lastly, we propose a series of testable predictions for how sex steroids impact sleep events and sleep-dependent cognition across the three major reproductive stages in women (reproductive years, menopause transition, and post-menopause).

Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

“…Earlier REM onset ( 15 ), reduced REM ( 13 , 16-20 ), and increased SWS ( 17 ) are observed during the luteal phase of some studies, whereas others report no differences ( 13 , 21 , 22 ) ( Fig. 2 ; comprehensive reviews are provided by others ( 11 , 12 , 14 , 23 )). The rate of change rather than absolute hormone levels may alter sleep, as evidenced by the association between decreasing E2/P levels during the late luteal phase and reduced SWS ( 20 ).…”

“…2 , Reproductive Years) ( 10 ). Cross-sectional studies comparing women in follicular to luteal phase report no group differences in sleep latency, waking after sleep onset (WASO), and sleep efficiency (SE; % time asleep in bed) ( 11-14 ). Earlier REM onset ( 15 ), reduced REM ( 13 , 16-20 ), and increased SWS ( 17 ) are observed during the luteal phase of some studies, whereas others report no differences ( 13 , 21 , 22 ) ( Fig.…”

Rapid eye movement fragmentation, not slow‐wave sleep, predicts neutral declarative memory consolidation in posttraumatic stress disorder

“…We did not gather information about participants’ menstrual cycle phase. Previous research suggests that variability in levels of sex hormones affects sleep‐dependent memory consolidation (Baker et al., ). For instance, in premenopausal women consolidation is optimized during the mid‐luteal phase of the cycle (Genzel et al., ).…”

Competitive dynamics underlie cognitive improvements during sleep

“…Limitations of this study include using a convenience sample of both men and women, and a lack of hormonal status among the young women, which can have an impact on cardiac vagal activity (see Schmalenberger et al, 2019 for a review) and sigma activity (Baker et al, 2019). Future studies examining hormonal fluctuation are needed to understand the interaction between central sigma and ANS profiles during sleep and their impact on cognition.…”