Center for Health Sciences, SRI International, Menlo Park, CA 94025, USA; Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa.
UC Irvine, Department of Cognitive Sciences, Irvine, CA 92697, USA.
Neurobiol Learn Mem. 2019 Apr;160:118-131. doi: 10.1016/j.nlm.2018.03.017. Epub 2018 Mar 21.
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).
年龄和性别是阿尔茨海默病的三个主要危险因素（载脂蛋白 E4 等位基因是第三个）之一，女性在 75 岁以后患阿尔茨海默病的风险是男性的两倍。在年轻和老年成年人中，广泛的认知技能中都表现出了性别差异，并且有证据表明性激素，尤其是雌二醇，在保护女性认知能力下降方面发挥作用。睡眠也可能是预防与年龄相关的认知能力下降的保护因素，因为特定的电生理睡眠事件（例如，睡眠纺锤波/慢波耦合）对于离线记忆巩固至关重要。此外，对年轻女性的研究表明，在月经周期的不同阶段，睡眠事件和睡眠依赖性记忆巩固会出现波动，这与性激素水平有关。一个被低估的可能性是，这两个保护因素（性激素和睡眠）之间可能存在重要的相互作用，这种相互作用可能在女性的整个生命周期中对认知处理（特别是记忆）的日常波动中起作用。在这里，我们总结了当前关于女性一生中性激素对睡眠和认知的影响的知识，特别强调了睡眠依赖性记忆处理。我们进一步指出了知识上的差距，需要进一步的实验研究来充分了解性激素和认知的复杂而不断变化的情况。最后，我们提出了一系列可测试的预测，说明性激素如何在女性的三个主要生殖阶段（生育期、绝经过渡期和绝经后）影响睡眠事件和睡眠依赖性认知。
