Changes in Sleep and Cognition in Older Women

描述(由申请人提供)：在SOF睡眠和认知研究的前5年，我们使用了客观测量的睡眠特征，包括手腕活动记录仪(n=3,161)和夜间家庭多导睡眠记录仪(n=461)，主要在社区居住的老年妇女中获得。在这些女性中，一组在五年后完成了一系列扩大的认知功能测试，并被归类为正常、轻度认知障碍。 或是痴呆症。我们证明了睡眠的几个特征(包括睡眠呼吸紊乱、睡眠质量和昼夜休息-活动节律)与事故风险有关。 轻度认知障碍或痴呆症，认知功能下降。这些新的发现对可能的认知障碍的预防和治疗具有重要的意义。我们现在提出一种经济有效的方法，扩大由SOF睡眠和认知研究支持的最初数据和样本的价值，以系统地解决专注于睡眠不良和认知障碍联系机制的新假说。此外，我们将延长对最初队列的跟踪，以确定睡眠特征和认知功能与其他与年龄相关的重要结果之间的独立关联。因此，我们提议的更新的目标包括：1)使用最近从SOF队列获得的表型和全基因组遗传数据，确定睡眠特征和认知结果的候选区域、基因和路径；2)测试睡眠不良与老年女性代谢功能障碍的横向和纵向变化有关的假设，以及代谢功能障碍中介睡眠不良和认知结果之间的关联；3)对多导睡眠图脑电信号进行频谱分析，以探索新的睡眠暴露(包括增量睡眠量、慢波活动消散率和纺锤频率活动)与5年随访期间代谢功能障碍和炎症的横断面和纵向变化以及与认知损害的发病之间的关系；以及4)确定睡眠特征和认知损害与发生的年龄相关结果(包括功能下降、疗养院安置和跌倒风险)之间的独立关联。这种更新应用产生的新信息有可能为开发新的治疗方法提供信息，以防止老年人认知功能的下降。此外，我们将利用SOF研究中对关键年龄相关结果的持续跟踪来确定睡眠和认知是否与这些疾病的风险独立相关。最终，我们的结果可能会强调在老年人中保持健康睡眠特征的重要性，以防止与衰老相关的认知和身体功能下降。 公共卫生相关性：我们之前已经证明，睡眠障碍和/或障碍与发展认知功能问题的风险有关。我们的新目标将探索这些发现的几种可能的解释，包括共同的遗传因素，可以在血液中测量的代谢功能的标记物，以及从夜间睡眠研究中获得的脑波数据产生的新测量。我们还将把睡眠和认知功能与结果联系起来，包括摔倒、功能下降和养老院安置。

DESCRIPTION (provided by applicant): In the first 5 years of the SOF Sleep and Cognition Study, we utilized objectively measured characteristics of sleep, including wrist actigraphy (n=3,161) and overnight in-home polysomnography (n=461) obtained in primarily community-dwelling older women. Among these women, a subset completed an expanded battery of cognitive function tests five years later and were classified as normal, mild cognitive impairment, or dementia. We demonstrated that several characteristics of sleep (including sleep disordered breathing, sleep quality, and circadian rest-activity rhythms) are associated with risk of incident mild cognitive impairment or dementia, and decline in cognitive function. These novel findings have important implications for the possible prevention and treatment of cognitive impairment. We now propose a cost-effective approach of extending the value of the initial collection of data and specimens supported by the SOF Sleep and Cognition Study to systematically address novel hypotheses focused on the mechanisms linking poor sleep and cognition. In addition, we will extend our follow-up of the initial cohort to identify the independent associations between sleep characteristics and cognitive function with other important age-related outcomes. Thus, the aims of our proposed renewal include: 1) To identify candidate -regions, -genes, and -pathways for both sleep characteristics and cognitive outcomes using recently obtained phenotypic and genome-wide genetic data from the SOF cohort; 2) To test the hypothesis that poor sleep is associated with both cross-sectional and longitudinal changes in metabolic dysfunction among older women, and that metabolic dysfunction mediates associations between poor sleep and cognitive outcomes; 3) To perform spectral analysis of the polysomnography EEG signal to explore associations between novel sleep exposures (including amounts of delta sleep, dissipation rates of slow wave activity, and spindle-frequency activity) with cross-sectional and longitudinal changes in metabolic dysfunction and inflammation, and with onset of cognitive impairment during 5 years of follow-up; and 4) To determine the independent associations of sleep characteristics and cognitive impairment with incident age-related outcomes including functional decline, nursing home placement, and risk of falls. The new information resulting from this renewal application has the potential to inform the development of new treatments to prevent decline in cognitive function in older adults. In addition, we will take advantage of ongoing follow-up for key age-related outcomes in the SOF study to determine whether sleep and cognition are independently related to risk for these conditions. Ultimately, our results may highlight the importance of maintaining healthy sleep characteristics in older adults to prevent the decline in cognitive and physical function associated with aging. PUBLIC HEALTH RELEVANCE: We have previously shown that sleep disorders and/or disturbances are related to the risk of developing problems with cognitive function. Our new aims will explore several possible explanations for these findings, including common genetic factors, markers of metabolic function which can be measured in blood, and new measures generated from brain wave data obtained during overnight sleep studies. We will also link sleep and cognitive function with outcomes including falls, functional decline and nursing home placement.