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

项目摘要 睡眠呼吸紊乱(SDB)和昼夜休息/活动节律改变(CRAR)越来越多 被认为是阿尔茨海默病和相关痴呆症的危险因素。肥胖与2型糖尿病(T2D) 是导致不良认知结果的主要生活方式风险因素，并与SDB和昼夜节律密切相关 改装。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，在患有T2D的老年超重或肥胖患者中还没有得到很好的研究，这些人已经 易受认知能力下降的影响。前瞻研究的拟议辅助调查将量化 SDB和CRAR(通过家庭睡眠测试和手腕动作)，并将使用经过验证的电话 认知测评方案在1500名前瞻参与者中，对SDB和更改的环节进行评估 有认知能力下降和临床症状的CRAR：轻度认知障碍、阿尔茨海默氏症 疾病和阿尔茨海默病相关疾病。我们将调查20年来的糖尿病 控制和体重轨迹，以及载脂蛋白ε4携带者状态作为潜在的效果修饰物，并探索血液 阿尔茨海默病的基本生物标记物(Aβ42/Aβ40、Total tau、pTau181和nfl)。最后，我们将利用 Look Forward的随机对照试验设计，以检查被随机分配到 针对饮食和体力活动的强化生活方式干预(ILI)(与糖尿病支持和教育 (DSE控制条件)在以后的生活中表现出更低的SDB率和更健壮、更少的相位延迟CRR。 我们将确定这些SDB/昼夜节律特征的差异是否与维护有关 在老年人的认知功能方面。这项研究的结果-由一组调查人员进行， 在衰老、睡眠、糖尿病、认知能力下降和阿尔茨海默氏症方面的专业知识-将促进我们的 了解SDB和CRAR改变如何影响患有T2D和T2D的老年人的脑健康 超重/肥胖，以及生活方式干预是否对睡眠/昼夜节律健康产生持久影响 在这一高危人群中转化为持续的大脑健康。

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.