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

睡眠和疼痛对阿尔茨海默病相关生物标志物的影响：识别认知功能正常至轻度受损女性的可改变危险因素

• 批准号: 10289504
• 负责人: Christina S McCrae
• 金额: $ 38.01万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10289504
• 关键词: Activities of Daily Living; Address; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Arousal; Attention; Attenuated; Behavior Therapy; Biological Markers; Brain region; C-reactive protein; Chronic Insomnia; Cognition; Cognitive; Cognitive Therapy; Data; Diagnosis; Education; Estradiol; Family; Female; Fibrinogen; Fibromyalgia; Functional Magnetic Resonance Imaging; Funding; Future; Genotype; Gonadal Steroid Hormones; Healthcare Systems; Hormones; Impaired cognition; Inflammation; Inflammatory; Infrastructure; Interleukin-6; Intervention; Measures; Medial; Memory; Menopause; Modeling; Nerve Degeneration; Neuraxis; Neurodegenerative Disorders; Neuronal Plasticity; Pain; Painless; Parents; Persons; Phase; Populations at Risk; Prefrontal Cortex; Public Health; Randomized; Randomized Clinical Trials; Recording of previous events; Reporting; Research; Research Support; Risk; Risk Factors; Role; Sampling; Sleep; Sleeplessness; Stimulus; Stress; Temporal Lobe; Testing; Testosterone; United States National Institutes of Health; Woman; Women' s Group; aged; apolipoprotein E-4; base; biopsychosocial; central sensitization; chronic pain; chronic widespread pain; cognitive function; cognitive performance; daily functioning; dementia risk; executive function; higher education; improved; instrumental activity of daily living; men; mild cognitive impairment; modifiable risk; novel; poor sleep; processing speed; recruit; relating to nervous system; screening; sex; tau Proteins

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.

项目概要 该补充剂将增加对可改变的阿尔茨海默病相关危险因素（睡眠、疼痛、觉醒）的了解， 及其与阿尔茨海默病相关生物标志物、认知和日间功能的关联和相互作用 三组中老年女性，其特征为：纤维肌痛和失眠 (FMI)、亚临床睡眠和疼痛 女性患阿尔茨海默氏症的风险更高 (2 倍)，而且大多数女性患有轻度认知障碍 (SPC) 或轻度认知障碍 (MCI)。 大多数（2/3）患有阿尔茨海默病的美国人是女性，慢性疼痛、睡眠质量差和 MCI 都是独立的。 与神经退行性疾病的更大风险以及与阿尔茨海默病相关的生物标志物水平增加有关 疾病（淀粉样蛋白 β-Aβ、tau）和炎症（C 反应蛋白-CRP、IL-6）因此，这些组是研究的理想选择。 这些因素并解决对其关联机制及其程度缺乏了解的问题 哪些可改变的因素（睡眠、疼痛、觉醒）可能相互作用，以减轻阿尔茨海默病的风险、发病或进展。 母研究是 NIH/NINR 资助的随机临床试验 (RCT)，重点关注睡眠和睡眠的机制作用。 我们的团队目前不专注于阿尔茨海默病的研究。 研究，并且母体试验并没有关注阿尔茨海默氏病，尽管如此，它提供了一个独特的机会。 检查父母测量的可改变的阿尔茨海默病相关因素之间的关联和相互作用 试验（睡眠、疼痛、觉醒）和阿尔茨海默病相关的生物标志物、认知和日间功能测量 该补充剂是我们团队开发阿尔茨海默病的重要第一步。 研究重点基于生物心理社会模型，其中睡眠、疼痛和觉醒与阿尔茨海默病的关联 疾病相关的生物标志物、认知和日间功能受性激素、APOE 基因型、年龄和 该补充利用了家长试验的基础设施、数据和特征良好的 FMI 样本。 30 名患有 FMI 的女性和 60 名患有 SCP 的女性将被招募作为母试验基线筛查的补充。 此外，还将招募 30 名患有 MCI 的女性作为新样本。 本补充测试了两个具体目标：目标 1 和 2 检查睡眠、疼痛、 觉醒和阿尔茨海默病相关的生物标志物、认知和日间功能，以及性激素对它们的调节， 患有 FMI、SPC 或 MCI 的女性的 APOE 基因型、年龄和教育程度，而这些目标涉及在 FMI、SPC 或 MCI 期间收集的数据。 在家长试验的筛选阶段，家长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，因此是一个探索性目标。 研究 CBT-I 减轻睡眠、疼痛和觉醒对阿尔茨海默病相关生物标志物影响的潜力 拟议的生物心理社会模型的结果将用于支持未来针对阿尔茨海默病的 R01 提案。 公共卫生影响：将睡眠、疼痛和觉醒确定为具有很大缓解潜力的干预目标 阿尔茨海默病的风险、发病或进展对患有痴呆症或有痴呆症风险的人具有重要影响，他们的 家庭和美国医疗保健系统。