Cognitive Aging, Brain Morphology, and Arrhythmias in Hispanics/Latinos: Implications for Prevention and Management of Alzheimer's Disease-Related Dementias

阿尔茨海默病（AD）和AD相关痴呆症（ADRD）预计将影响1.15亿人 到2050年在全球范围内。血管对认知障碍和痴呆的贡献（VCID）-一种主要类型的 ADRD是NIH的一个主要研究重点，它呼吁需要进行跨学科的预防研究。 寿命和不同人群（ADRD峰会2019）。认识不足但与VCID相关，先前 研究表明，心律失常与认知功能低下和AD/ADRD风险增加有关。 然而，目前的知识心律失常的神经认知影响是缺乏在增长最快的种族， 美国的一个群体--西班牙裔/拉丁裔--预计将对预计的 轻度认知障碍（MCI）和ADRD的患病率增加。因此，可靠和全面的数据 西班牙裔/拉丁裔人群中心律失常的患病率和神经认知影响。 此外，从预防的角度来看，虽然先前的研究表明，改变生活方式和 心血管疾病（CVD）危险因素与ADRD风险和心律失常风险和负担相关， 尚不清楚优化生活方式/CVD风险因素是否可以减轻糖尿病与ADRD的关系。到 为了解决上述知识差距，我们将应用Zio ECONDIX XT贴片-一种非侵入性的非卧床持续性 西班牙裔社区健康研究/研究中的ECG监测仪-约5，000例受试者（年龄≥45岁） 拉丁美洲人（HCHS/SOL）在2022-24年（与访视3同时），并利用HCHS/SOL和相关的丰富数据 辅助研究：神经认知评估、裁定的MCI和ADRD、脑MRI、心脏MRI， 生活方式/CVD风险因素，包括7天基于加速计的体力活动、肥胖测量和血液 压力我们假设，在西班牙裔/拉丁裔成人中，心律失常频率较高与以下因素相关： MCI或ADRD的发生率更高，认知能力下降更严重，脑梗死和小血管缺血更多 疾病和脑容量降低。这些关联将独立于CVD和心血管疾病 结构/功能，并将在那些不太理想的（与更理想的）生活方式/CVD风险因素更明显 轨迹我们将评估这些目标：目标1：确定心律失常的患病率和频率， 使用动态心律监测的西班牙裔/拉丁裔成人，目标2：评价 心律失常伴认知功能改变与MCI或ADRD事件，目的3：评估 心律失常与基于脑MRI的血管性脑损伤标记物。重要的是，对于每个目标，我们将 通过先前10年的生活方式/CVD风险因素轨迹检查相关性的一致性。这 该项目将结合联合收割机卓越和互补的科学专业知识，可穿戴和成像技术， 严格的流行病学和分析方法，并利用现有的NIH队列来完善VCID 范式，克服AD/ADRD和少数民族健康研究中的关键障碍，从而实现可持续发展。 并对公共卫生和临床实践产生强大影响。

Alzheimer’s Disease (AD) and AD-Related Dementias (ADRD) are projected to affect 115 million people worldwide by 2050. Vascular contributions to cognitive impairment and dementia (VCID)—a primary type of ADRD—is a major research focus for the NIH, which has called for the need for studies of prevention across the lifespan and in diverse populations (ADRD summit 2019). Underrecognized but relevant to VCID, prior research indicates that arrhythmias are associated with lower cognitive function and greater risk of AD/ADRD. However, current knowledge of arrhythmias’ neurocognitive impact is lacking in the fastest growing ethnic group in the USA—Hispanics/Latinos—who are anticipated to contribute disproportionately to the projected increase in prevalence of mild cognitive impairment (MCI) and ADRD. Thus, robust and comprehensive data on prevalence and neurocognitive impact of arrhythmias in Hispanics/Latinos are critically needed. Furthermore, from a prevention standpoint, although prior research shows that modifiable lifestyle and cardiovascular disease (CVD) risk factors are related to ADRD risk and arrhythmia risk and burden, it is unknown whether optimizing lifestyle/CVD risk factors can mitigate the arrhythmia-ADRD relationship. To address the foregoing knowledge gaps, we will apply the ZioXT Patch—a non-invasive ambulatory continuous ECG monitor—to ~5,000 participants (age ≥45 years) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) in 2022-24 (concurrent with Visit 3) and leverage the rich data in HCHS/SOL and related ancillary studies: neurocognitive assessment, adjudicated MCI and ADRD, brain MRI, cardiac MRI, lifestyle/CVD risk factors including 7-day accelerometer-based physical activity, adiposity measures, and blood pressure. We hypothesize that in Hispanic/Latino adults, higher arrhythmia frequency will be associated with higher incidence of MCI or ADRD, greater cognitive decline, more brain infarcts and small vessel ischemic disease, and lower brain volumes. These associations will be independent of CVD and cardiac structure/function and will be more evident in those with less optimal (vs. more optimal) lifestyle/CVD risk factor trajectories. We will evaluate these aims: Aim 1: Define the prevalence and frequency of arrhythmias in Hispanic/Latino adults using ambulatory heart rhythm monitoring, Aim 2: Evaluate the association of arrhythmias with change in cognitive function and incident MCI or ADRD, Aim 3: Assess the association of arrhythmias with markers of vascular brain injury based on brain MRI. Importantly, for each Aim, we will examine the consistency of associations by antecedent 10-year lifestyle/CVD risk factor trajectories. This project will combine exceptional and complementary scientific expertise, wearable and imaging technology, rigorous epidemiological and analytical methods, and leverage an existing NIH cohort to refine the VCID paradigm and overcome critical barriers in AD/ADRD and minority health research, thus achieving a sustained and powerful impact on public health and clinical practice.