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

项目概要 睡眠呼吸障碍 (SDB) 和昼夜休息/活动节律改变 (CRAR) 日益严重 被认为是阿尔茨海默病和相关痴呆症的危险因素。肥胖和 2 型糖尿病 (T2D) 是导致认知结果不佳的主要生活方式风险因素，并且与 SDB 和昼夜节律密切相关 变更。 SDB 和改变的 CRAR 在促进认知能力下降和痴呆风险中的作用， 然而，尚未在患有 T2D 的老年超重或肥胖个体中进行充分研究，这些人已经 容易出现认知能力下降。拟议的前瞻性研究的辅助调查将量化 SDB 和 CRAR（通过家庭睡眠测试和腕部体动记录仪）并将使用经过验证的电话 对 1,500 名 Look AHEAD 参与者进行认知评估协议，以评估 SDB 和改变的联系 具有认知能力下降的 CRAR 和判定的临床状况：轻度认知障碍、阿尔茨海默病 该队列中的疾病和阿尔茨海默氏病相关疾病。我们将调查约 20 年的糖尿病 控制和体重轨迹，以及 APOE ε4 携带者状态作为潜在的效果调节剂，并探索血液 基于阿尔茨海默病的生物标志物（Aβ42/Aβ40、总 tau、pTau181 和 NfL）。最后，我们将利用 Look AHEAD 的随机对照试验设计旨在检验被随机分配到 针对饮食和身体活动的强化生活方式干预 (ILI)（相对于糖尿病支持和教育） （DSE）控制条件）在以后的生活中表现出较低的 SDB 率和更稳健、相位延迟更少的 CRAR。 我们将确定这些 SDB/昼夜节律特征的差异是否与维护有关 老年认知功能的影响。这项研究的结果——由一组研究人员进行 在衰老、睡眠、糖尿病、认知能力下降和阿尔茨海默氏病方面的专业知识将推动我们的进步 了解 SDB 和改变的 CRAR 如何影响患有 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/昼夜节律健康产生持久影响 转化为这一高危人群的持续大脑健康。

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.