Look AHEAD Sleep: Sleep-disordered breathing, circadian rest/activity rhythms, and the risk of Alzheimer's disease and related dementias in Look AHEAD

Look AHEAD 睡眠：Look AHEAD 中的睡眠呼吸障碍、昼夜节律休息/活动节律以及阿尔茨海默病和相关痴呆症的风险

• 批准号: 10468298
• 负责人: Kathleen M Hayden
• 金额: $ 214.35万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10468298
• 关键词: Adult; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Apnea; Biological Assay; Body Weight decreased; Caloric Restriction; Cardiovascular system; Characteristics; Circadian Rhythms; Classification; Clinical; Cognition; Cognitive; Data; Diabetes Mellitus; Diet; Disease; Education; Elderly; Event; Exhibits; Goals; Health; Home; Hour; Hypoxemia; Impaired cognition; Incidence; Investigation; Life Style; Life Style Modification; Light; Link; Long-Term Effects; Maintenance; Measures; Metabolic Diseases; Modification; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Oxygen; Participant; Persons; Phase; Physical activity; Physiological Processes; Population; Populations at Risk; Prevalence; Prevention; Protocols documentation; Race; Randomized; Randomized Controlled Trials; Recording of previous events; Research Personnel; Rest; Risk; Risk Factors; Role; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Fragmentations; Subgroup; Telephone; Testing; Translating; Vulnerable Populations; Weight; Weight Gain; Wrist; actigraphy; adjudicate; adult obesity; aged; apolipoprotein E-4; arm; blood-based biomarker; brain health; carrier status; circadian; cognitive function; cognitive performance; cognitive testing; cohort; dementia risk; diabetes control; ethnic minority; follow-up; glycemic control; indexing; lifestyle intervention; mild cognitive impairment; modifiable risk; neurofilament; obese person; sex; tau Proteins; treatment arm; trial design

Project Summary Sleep disordered breathing (SDB) and altered circadian rest/activity rhythms (CRARs) are increasingly recognized as risk factors for Alzheimer’s disease and related dementias. Obesity and type 2 diabetes (T2D) are leading lifestyle risk factors for poor cognitive outcomes, and are closely linked to SDB and circadian alterations. The roles of SDB and altered CRARs in the promotion of cognitive decline and dementia risk, however, have not been well studied in older overweight or obese individuals with T2D, who are already vulnerable to cognitive decline. The proposed ancillary investigation to the Look AHEAD Study will quantify SDB and CRARs (through home sleep testing and wrist actigraphy) and will use a validated telephone cognitive assessment protocol in 1,500 Look AHEAD participants, to evaluate the links of SDB and altered CRARs with cognitive decline and adjudicated clinical conditions: mild cognitive impairment, Alzheimer’s disease, and Alzheimer’s disease related disorders, in this cohort. We will investigate ~20-year diabetes control and weight trajectories, and APOE ε4 carrier status as potential effect modifiers, and explore blood based biomarkers of Alzheimer’s disease (Aβ42/Aβ40, total tau, pTau181, and NfL). Finally, we will leverage Look AHEAD’s randomized controlled trial design to examine whether participants who were randomized to an intensive lifestyle intervention (ILI) that targeted diet and physical activity (vs. a diabetes support and education (DSE) control condition) exhibit lower rates of SDB and more robust, less phase-delayed CRARs in later life. We will determine whether differences in these SDB/circadian characteristics are associated with maintenance of cognitive function in older adulthood. Results of this study—conducted by a team of investigators with expertise in aging, sleep, diabetes, and cognitive decline and Alzheimer’s disease—will advance our understanding of how SDB and altered CRARs affect brain health among older adults with T2D and overweight/obesity, and whether a lifestyle intervention produces durable effects on sleep/circadian health that translate into sustained brain health in this at-risk population.

项目摘要 睡眠不足的呼吸（SDB）和昼夜节律改变/活动节奏（crars）越来越多 被公认为是阿尔茨海默氏病和相关痴呆症的危险因素。肥胖和2型糖尿病（T2D） 是领先的生活方式危险因素，导致认知结果不佳，并且与SDB和昼夜节律密切相关 改变。 SDB的作用和改变了crar虫在促进认知能力下降和痴呆风险中的作用， 但是，在年龄较大的超重或肥胖的T2D的人中还没有很好地研究 容易受到认知能力下降的影响。拟议的辅助研究对未来的研究将量化 SDB和CRARS（通过家庭睡眠测试和手腕行为摄影），将使用经过验证的电话 认知评估协议中有1,500名观察参与者，以评估SDB的链接并更改 认知能力下降和调整临床状况的狂暴：轻度认知障碍，阿尔茨海默氏症 疾病和阿尔茨海默氏病有关的疾病，在该队列中。我们将调查约20年的糖尿病 控制和重量轨迹以及APOEε4载体状态作为潜在效应修饰符，并探索血液 基于阿尔茨海默氏病的生物标志物（Aβ42/Aβ40，Tau Tau，PTAU181和NFL）。最后，我们将利用 查看未来的随机对照试验设计，以检查随机分配到一个随机的参与者 针对饮食和体育锻炼的密集生活方式干预（ILI）（与糖尿病的支持和教育 （DSE）控制条件）在以后的生活中，SDB的较低率和更稳定的相差训练较低。 我们将确定这些SDB/昼夜节律特征的差异是否与维护有关 老年人的认知功能。这项研究的结果 - 由一个调查员团队与 衰老，睡眠，糖尿病和认知能力下降和阿尔茨海默氏病的专业知识 - 将进步我们 了解SDB和变化的训练如何影响T2D和T2D的老年人的大脑健康 超重/肥胖，以及生活方式干预是否会对睡眠/昼夜节律产生持久的影响 在这种高危人群中转化为持续的大脑健康。