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（ADRD）预计将影响1.15亿人

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.