Leveraging the 24-hour movement paradigm to preserve cognitive function and prevent Alzheimer's disease: The Multi-Ethnic Study of Atherosclerosis (MESA) 24H-ACT Study

摘要 阿尔茨海默病及相关痴呆症(ADRD)在美国是一种新的流行病。 黑人和西班牙裔男性和女性特别容易受到ADRD的影响。没有有效的预防措施 针对和优化应对ADRD的战略，到2060年，美国将有1400万成年人患有ADRD， 到2040年，相关的财政负担将达到5110亿美元。虽然体力活动一直是 被确认为一种可改变的保护性因素，可防止认知能力下降和延迟痴呆症的发病年龄 大多数证据是基于报道的对休闲时间中等到剧烈强度的体力活动的估计。 活性(MVPA)，这对这种复杂的行为表型提供了不完整的表征。 大约95%的清醒时间是久坐不动或进行光强度的体力活动；然而，有 探索这些不同强度类别对健康影响的研究有限。此外，只有不到10%的 成年人累积的MVPA足以达到建议的水平，少数人的MVPA患病率甚至更低 组。研究还表明，睡眠障碍，特别是睡眠持续时间和睡眠- 呼吸紊乱可能会增加认知障碍的风险。然而，这一系列证据仍然是 正在浮现。此外，黑人和西班牙裔成年人睡眠障碍的患病率比 白色的。尽管清醒和睡眠行为对优化认知韧性具有潜在的重要性， 它们的影响经常被孤立地研究。为了解决这些关键的研究差距，我们提出了多- 动脉粥样硬化24小时活动周期研究的种族研究(MESA 24H-ACT)，一项为期四年的辅助研究 梅萨。MESA 24H-ACT研究的总体目标是量化体力活动和睡眠的影响，通过 24小时运动模式，以保护认知功能和预防阿尔茨海默病。参与者 符合资格标准并同意参加的人(估计n=2,125人)将被包括在内。作为台地的一部分 24小时-ACT，我们建议为MESA增加7天加速度计和睡眠活动记录协议，以 客观地测量24小时活动周期(久坐行为、光强度体力活动、MVPA和 睡眠)。为了实现这些目标，这项研究将检查24小时活动周期行为的关联， 通过基于设备的测量确定，横断面与认知；脑血管疾病的标志物， 神经退行性变和淀粉样蛋白负担；以及MCI和痴呆的患病率(AIM 1)；自我检查 报告的24小时活动周期行为与全球认知功能的预期变化， 脑血管疾病和神经退行性变(AIM 2)；并阐明两者之间的双向关系 认知功能受损和超过12年的24小时活动周期。MESA 24H-ACT将解决当前 证据差距并提供经验证据，以加速向综合模型的范式转变 整合所有24小时运动行为，以优化不同种族/民族的大脑健康 人口。

ABSTRACT Alzheimer’s Disease and Related Dementias (ADRD) are an emerging epidemic in the United States (U.S.). Black and Hispanic men and women are particularly vulnerable to ADRD. Without effective prevention strategies to target and optimize resilience to ADRD, 14 million U.S. adults will be living with ADRD by 2060, with an associated financial burden of $511 billion by 2040. While physical activity has been consistently identified as a modifiable, protective factor to prevent cognitive decline and delay age of dementia onset, the majority of this evidence is based on reported estimates of leisure-time moderate to vigorous intensity physical activity (MVPA), which provides an incomplete characterization of this complex behavioral phenotype. Approximately 95% of waking hours are spent sedentary or in light intensity physical activity; however, there is limited research exploring the health impacts of these different intensity categories. Also, less than 10% of adults accumulate sufficient MVPA to meet recommendations, and this prevalence is even lower in minority groups. Studies have also demonstrated that sleep disturbances, particularly sleep duration and sleep- disordered breathing may increase risk of cognitive impairment. However, this body of evidence is still emerging. Further, Black and Hispanic adults have a higher prevalence of disordered sleep compared to Whites. Despite the potential importance of both waking and sleep behaviors to optimize cognitive resilience, their impacts are often studied in isolation. To address these critical research gaps, we propose the Multi- Ethnic Study of Atherosclerosis 24-Hour Activity Cycle Study (MESA 24H-ACT), a four-year ancillary study to MESA. The overall goal of the MESA 24H-ACT Study is to quantify the impact of physical activity and sleep via the 24-hour movement paradigm to preserve cognitive function and prevent Alzheimer’s disease. Participants who meet eligibility criteria and agree to participate (estimated n=2,125) will be included. As part of MESA 24H-ACT, we propose to augment MESA with a 7-day accelerometer and sleep actigraphy protocol to objectively measure the 24-hour activity cycle (sedentary behavior, light intensity physical activity, MVPA, and sleep). To accomplish these goals, this study will examine the associations of 24-hour activity cycle behaviors, ascertained via device-based measures, cross-sectionally with cognition; markers of cerebrovascular disease, neurodegeneration, and amyloid burden; and the prevalence of MCI and dementia (AIM 1); examine self- reported 24-hour activity cycle behaviors with prospective changes in global cognitive function, cerebrovascular disease and neurodegeneration (AIM 2); and elucidate the bidirectional relationship between impaired cognitive function and 24-hour activity cycles over 12 years. MESA 24H-ACT will address current evidence gaps and provide empirical evidence to accelerate a paradigm shift towards an integrated model that incorporates all 24-hour movement behaviors to optimize brain health across racially/ethnically diverse populations.