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.

项目摘要 这种补充剂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志物、认知和日间功能的关联和相互作用， 三组中老年女性的特征是：纤维肌痛和失眠（FMI），亚临床睡眠和疼痛 轻度认知障碍（MCI）。女性患阿尔茨海默病的风险更大（2倍）， 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 与神经退行性疾病的风险增加有关，与阿尔茨海默病相关的生物标志物水平增加 疾病（淀粉样蛋白β-A β，tau）和炎症（C反应蛋白-CRP，IL-6）。因此，这些群体是理想的研究 这些因素，并解决缺乏对它们之间联系的基本机制的了解， 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、发作或进展。 这项母研究是由NIH/NINR资助的随机临床试验（RCT），重点关注睡眠的机制作用， 慢性疼痛和疼痛相关神经可塑性的唤醒。我们的团队目前没有进行阿尔茨海默病的重点 研究，和父母的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 在这个补充中提出。这种补充剂是我们团队开发阿尔茨海默病的重要第一步 研究重点是基于生物心理社会模型，其中睡眠，疼痛和唤醒与阿尔茨海默氏症的联系 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 教育该补充利用了母试验的基础设施、数据和FMI的良好表征样本 的SCP。将从母试验的基线筛选中招募30名FMI女性和60名SCP女性进行补充 相位此外，还将招募30名患有MCI的妇女作为新样本。 本补充测试两个具体目标：目标1和2检查睡眠，疼痛， 唤醒和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， 患FMI、SPC或MCI的妇女的APOE基因型、年龄和教育虽然这些目标涉及在 在父母试验的筛选阶段，父母试验还检查了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、中枢敏感化和神经可塑性的影响。因此，一个探索性的目标 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的影响的潜力， 提出的生物心理社会模型。结果将用于支持未来的R01提案，重点是阿尔茨海默病。 公共卫生意义：将睡眠、疼痛和觉醒确定为具有高度缓解潜力的干预目标 阿尔茨海默病的风险、发作或进展对患有痴呆症或有患痴呆症风险的人具有重要意义， 家庭和美国医疗保健系统。