Contributions of Sleep and Pain to Alzheimer's Disease Related Biomarkers: Identifying Modifiable Risk Factors in Women with Normal to Mildly Impaired Cognitive Function

项目总结 这一补充将增加对可改变的阿尔茨海默病相关风险因素(睡眠、疼痛、觉醒)的理解， 以及它们与阿尔茨海默病相关生物标记物、认知和日间功能的关联和相互作用 三组中老年女性的特点是：纤维肌痛和失眠(FMI)，亚临床睡眠和疼痛 主诉(SPC)或轻度认知障碍(MCI)。女性患阿尔茨海默氏症的风险更大(2倍)，而且 大多数(2/3)患有阿尔茨海默病的美国人是女性。慢性疼痛、睡眠不佳和MCI是独立的 与更高的神经退行性疾病风险相关，以及与阿尔茨海默氏症相关的生物标志物水平增加 疾病(淀粉样β-Aβ，Tau)和炎症(C-反应蛋白，IL-6)。因此，这些群体是研究的理想对象 这些因素并解决了对其相互关联的机制缺乏了解的问题，以及 哪些可改变的因素(睡眠、疼痛、觉醒)可以相互作用来降低阿尔茨海默病的风险、发病或进展。 母研究是由NIH/NINR资助的随机临床试验(RCT)，重点是睡眠和睡眠的机制作用。 慢性疼痛的觉醒和疼痛相关的神经可塑性。我们的团队目前并不专注于阿尔茨海默氏症 研究，父母试验没有阿尔茨海默病的重点。尽管如此，它提供了一个独特的机会 检查在父母中测量的可改变的阿尔茨海默病相关因素之间的联系和相互作用 试验(睡眠、疼痛、觉醒)和阿尔茨海默病相关生物标记物、认知和日间功能测量 在本补编中提出。这种补充剂是我们团队开发阿尔茨海默氏症的重要第一步 基于生物心理社会模型的研究重点，在该模型中，睡眠、疼痛和觉醒与阿尔茨海默氏症有关 与疾病相关的生物标志物、认知和日间功能受性激素、载脂蛋白E基因、年龄和 教育。本补充利用了父试验的基础设施、数据和FMI的特征良好的样本 和SCP。30名患有FMI的女性和60名患有SCP的女性将被招募为父母试验基线筛查的补充 相位。此外，还将招募30名患有MCI的女性作为新样本。 本附录测试两个具体目标：目标1和目标2检查睡眠、疼痛、 觉醒、阿尔茨海默氏症相关的生物标志物、认知和日间功能，以及性激素对它们的调节， FMI、SPC或MCI女性的载脂蛋白E基因型、年龄和教育程度。虽然这些目标涉及在 父母试验的筛选阶段，父母试验还检查认知行为治疗对失眠的影响 (CBT-I)对患有FMI的女性的睡眠、疼痛、觉醒、中枢敏化和神经可塑性的影响。因此，一个探索性的目标 研究CBT-I对减轻睡眠、疼痛和觉醒对阿尔茨海默病相关生物标记物的影响的潜力 提出的生物-心理-社会模式。结果将被用来支持未来的R01提案，重点是阿尔茨海默病。 公共卫生影响：将睡眠、疼痛和觉醒确定为高潜力缓解的干预目标 阿尔茨海默病的风险、发病或进展对痴呆症患者或有痴呆症风险的人具有重要意义，他们的 家庭，以及美国的医疗体系。

PROJECT SUMMARY This supplement will increase understanding of modifiable Alzheimer’s disease related risk factors (sleep, pain, arousal), and their associations and interactions with Alzheimer’s disease related biomarkers, cognition, and daytime functioning in three groups of middle-to-older aged women characterized by: fibromyalgia and insomnia (FMI), subclinical sleep and pain complaints (SPC), or mild cognitive impairment (MCI). Women are at greater risk (2x) of Alzheimer’s disease, and the vast majority (2/3rds) of Americans with Alzheimer’s disease are women. Chronic pain, poor sleep, and MCI are independently associated with greater risk of neurodegenerative disorders, and increased levels of biomarkers associated with Alzheimer’s disease (amyloid beta-Aβ, tau) and inflammation (C-reactive Protein-CRP, IL-6). Thus, these groups are ideal for studying these factors and addressing the lack of understanding of the mechanisms underlying their association and the degree to which modifiable factors (sleep, pain, arousal) may interact to mitigate Alzheimer’s disease risk, onset or progression. The parent study, a NIH/NINR funded randomized clinical trial (RCT), focuses on the mechanistic roles of sleep and arousal in chronic pain and pain-related neural plasticity. Our team does not currently conduct Alzheimer’s disease focused research, and the parent trial does not have an Alzheimer’s disease focus. Nonetheless, it offers a unique opportunity to examine the associations and interactions amongst the modifiable Alzheimer’s disease related factors measured in the parent trial (sleep, pain, arousal) and the Alzheimer’s disease related biomarkers, cognition, and daytime functioning measures proposed in this supplement. This supplement is an important first step for our team to develop an Alzheimer’s disease research focus based on a biopsychosocial model in which the associations of sleep, pain, and arousal with Alzheimer’s disease related biomarkers, cognition, and daytime functioning are moderated by sex hormones, APOE genotype, age, and education. This supplement takes advantage of the parent trial’s infrastructure, data, and well-characterized samples of FMI and SCP. 30 women with FMI and 60 with SCP will be recruited for the supplement from the parent trial’s baseline screening phase. Additionally, a new sample of 30 women with MCI will be recruited. This supplement tests two specific aims: Aims 1 and 2 examine the associations and interactions amongst sleep, pain, arousal, and Alzheimer’s related biomarkers, cognition, and daytime functioning, and their moderation by sex hormones, APOE genotype, age, and education in women with FMI, SPC, or MCI. While these aims involve data collected during the screening phase of the parent trial, the parent trial also examines the impact of cognitive behavioral treatment for insomnia (CBT-I) on sleep, pain, arousal, central sensitization, and neural plasticity in women with FMI. Thus, an Exploratory Aim investigates CBT-I’s potential to mitigate the impact of sleep, pain, and arousal on the Alzheimer's related biomarkers in the proposed biopsychosocial model. Results will be used to support future R01 proposals focused on Alzheimer’s disease. Public Health Implications: Identification of sleep, pain, and arousal as intervention targets with high potential to mitigate Alzheimer’s disease risk, onset or progression has important implications for persons with or at risk for dementia, their families, and the US healthcare system.