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。血管对认知损害和痴呆的贡献(VCID)--一种主要类型 ADRD-是美国国立卫生研究院的一个主要研究重点，该机构呼吁需要对整个 不同人群的寿命(2019年ADRD峰会)。未被认可，但与VCID相关，之前 研究表明，心律失常与认知功能低下和患AD/ADRD的风险更大有关。 然而，目前关于心律失常对神经认知的影响的知识在增长最快的民族中是缺乏的。 美国的群体-拉美裔/拉美裔-预计他们对预测的贡献不成比例 轻度认知障碍(MCI)和ADRD的患病率增加。因此，稳健和全面的数据 关于拉美裔/拉丁裔心律失常的患病率和神经认知影响的研究是迫切需要的。 此外，从预防的角度来看，尽管先前的研究表明，可改变的生活方式和 心血管疾病(CVD)的危险因素与ADRD风险和心律失常的风险和负担有关， 尚不清楚优化生活方式/心血管危险因素是否可以缓解心律失常与ADRD的关系。至 为了解决上述知识差距，我们将应用ZIOXT补丁-一种非侵入性的可卧床连续 对西班牙裔社区健康研究/研究的约5,000名参与者(年龄≥45岁)进行心电监测 2022-24年拉丁美洲人(HCHS/SOL)(同时访问3)，并利用HCHS/SOL和相关的丰富数据 辅助研究：神经认知评估，判定的MCI和ADRD，脑MRI，心脏MRI， 生活方式/心血管疾病的危险因素包括基于7天加速计的体力活动、肥胖测量和血液 压力。我们假设，在西班牙裔/拉丁裔成年人中，较高的心律失常频率将与 MCI或ADRD的发生率更高，认知功能减退更严重，脑梗塞和小血管缺血更多 疾病，以及较低的脑容量。这些关联将独立于心血管疾病和心脏疾病 结构/功能，在那些生活方式/心血管疾病风险因素不太理想(与更理想)的人中将更加明显 轨迹。我们将评估这些目标：目标1：确定年内心律失常的发生率和频率 使用动态心率监测的西班牙裔/拉丁裔成年人，目标2：评估 心律失常与认知功能改变和MCI或ADRD事件的关系，目标3：评估 脑部MRI显示血管脑损伤标志物的心律失常。重要的是，对于每个目标，我们都会 通过之前10年的生活方式/心血管疾病风险因素轨迹来检验相关性的一致性。这 该项目将结合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和少数群体健康研究中的关键障碍，从而实现可持续的 并对公共卫生和临床实践产生强大的影响。

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.