Examining Sleep, Circadian Rhythms, and Cognitive Functioning in Older Adults at Risk of Dementia

项目总结/摘要 阿尔茨海默病（AD）是一种进行性神经退行性疾病，其导致认知和功能障碍， 是老年人死亡和残疾的主要原因。由于没有治愈AD的方法， 目前的研究集中在了解早期认知和行为变化，以帮助早期诊断 和治疗实施。老年人容易经历认知变化和睡眠变化 功能和昼夜节律，调节24小时内生理和行为的时间。 睡眠和昼夜节律紊乱对认知功能产生负面影响， 认知能力下降和AD痴呆的风险增加。主观认知下降（SCD）是最早的 在客观轻度认知障碍（MCI）之前可观察到的变化，并且通常表明需要 认知评价关于成人昼夜节律紊乱的研究很少 患有SCD，并且还不清楚昼夜节律紊乱如何与SCD的变化相关。 认知功能的变化与其他已知与睡眠和认知有关的因素的关联 功能，如压力，也在这一组中研究不足。检查昼夜节律的时间，他们的 与认知功能的关联，以及压力对SCD中这些关系的影响可能揭示 针对昼夜节律计时系统的认知衰退的预测因素或治疗。 这项拟议中的研究将检查50岁以上的成年人的昼夜节律时间和认知功能， (a)正在经历SCD，（B）患有MCI，和（c）认知完整。暗光褪黑激素起效（DLMO） 测试，活动记录和神经心理学的措施将被用来比较昼夜节律的时间， 这些组的认知功能（N=90;每组30）。本研究旨在探讨：（1） 研究组之间的昼夜节律时间差异;（2）昼夜节律时间之间的关联 和认知功能在这三个群体;（3）是否感知压力缓和这些 协会.假设患有SCD和MCI的成年人将表现出先进的昼夜节律阶段，增加 与年龄匹配的认知完整的成年人相比，碎片化和睡眠不规律增加;这些 昼夜节律紊乱与客观神经心理学的认知表现较差有关 测试;这些关联将由压力评级来调节。通过这项奖学金，申请人将 在睡眠和神经心理学研究方法方面获得宝贵的经验和实践培训， 分析，使她能够全面检查认知能力下降和AD的睡眠相关风险。 此外，她将通过在波士顿大学布里格姆分校的培训和研究工作建立一个网络， 妇女医院和马萨诸塞州总医院。这些经历将为她提供 随着对老龄化人群中认知和睡眠之间关系的深入了解， 为她的职业生涯做好准备，作为与年龄相关的认知能力下降的预测因素和结果的临床研究者。

PROJECT SUMMARY / ABSTRACT Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to cognitive and functional impairment, and is a leading cause of death and disability in aging populations. As there is no cure for AD, current research is focused on understanding early cognitive and behavioral changes to aid in earlier diagnosis and treatment implementation. Older adults are prone to experiencing cognitive changes and changes in sleep function and circadian rhythms, which regulate timing of physiology and behavior across the 24-hour day. Sleep and circadian rhythm disturbances negatively impact cognitive functioning, and are associated with increased risk of cognitive decline and AD dementia. Subjective cognitive decline (SCD) is one of the earliest observable changes preceding objective mild cognitive impairment (MCI), and often signals the need for a cognitive evaluation. There is a paucity of research examining circadian rhythm disturbances in adults experiencing SCD, and it is not well understood how circadian rhythm disturbances may relate to changes in cognitive functioning in this population. Associations with other factors known to relate to sleep and cognitive functions, such as stress, are also understudied in this group. Examining circadian rhythm timing, their associations with cognitive functions, and the influence of stress on these relations in SCD may reveal predictive factors or treatments of cognitive decline targeted to the circadian timing system. The proposed study will examine circadian rhythm timing and cognitive functioning in adults over 50 who (a) are experiencing SCD, (b) have MCI, and (c) are cognitively intact. Dim light melatonin onset (DLMO) testing, actigraphy, and neuropsychological measures will be used to compare circadian rhythm timing and cognitive functioning across these groups (N=90; 30 in each group). This study aims to examine: (1) differences in circadian rhythm timing between study groups; (2) associations between circadian rhythm timing and cognitive functioning in these three groups; and (3) whether perceived stress moderates these associations. It is hypothesized that adults with SCD and MCI will exhibit advanced circadian phase, increased fragmentation, and increased sleep irregularity compared to age-matched cognitively intact adults; that these circadian disruptions will be associated with worse cognitive performance on objective neuropsychological tests; and these associations will be moderated by stress ratings. Through this fellowship, the applicant will gain valuable experience and hands-on training in sleep and neuropsychological research methods and analyses, enabling her to comprehensively examine sleep-related risks of cognitive decline and AD. Furthermore, she will build a network through training and research engagement at Boston University, Brigham and Women’s Hospital, and Massachusetts General Hospital. Together, these experiences will provide her with a deeper understanding of the relations between cognition and sleep in aging populations, and will prepare her for a career as a clinical investigator of predictors and outcomes of age-related cognitive decline.