Cognitive Dysfunction in Atrial Fibrillation

摘要 心房颤动（AF）是最常见、最昂贵的心律失常，影响超过600万人 死亡率增加了两倍作为一个主要的公共卫生问题，AF 严重后果的中风和心力衰竭，是一个独立的危险因素， 认知障碍（MCI）和阿尔茨海默型痴呆（AD）。AF相关机制 MCI/AD尚不清楚，但可能的多因素机制包括脑灌注不足， 亚临床脑缺血、血管炎症、海马脑萎缩或遗传性 因素改善口服抗凝剂（OAC）药物的使用理论上可以减少 亚临床脑缺血，但研究如何，或如果，OACs的影响进展速度， 认知能力下降的结果相互矛盾。虽然OAC可以减少脑缺血， 这些药物增加了脑出血的风险，也与认知能力下降有关。 有新的OAC药物，降低脑缺血和出血的发生率优于 华法林称为非维生素K抑制剂（NOAC）。拟议研究的目标是 检查认知能力下降的进展速度（使用神经心理学和功能 在美国国立卫生研究院（NIH）赞助的国家研究中， 阿尔茨海默氏症协调中心（NACC）数据集。这项纵向研究大约 42，000名社区居住成年人包括患有一系列认知障碍的受试者 （正常、MCI和痴呆）。既往AF相关MCI/AD的一个主要方法学问题 研究是不一致的利用各种神经心理措施，NACC 数据库包括。我们还将比较接受OAC治疗的AF患者的认知功能下降率， 未使用OAC和使用NOAC与华法林的患者。此外，我们将探索AD 神经病理学（即，AF患者中的神经系统缠结）、血管性痴呆和混合性AD 与无房颤的患者进行比较。女性患MCI的风险高于男性 和AD，AF相关卒中也是如此，表明性别作为一个重要因素， 生物变量NACC数据库提供了一个独特而丰富的机会来检查AF 和OAC对从正常认知到MCI到AD的进展速率的影响。理解 更多地了解房颤相关的认知功能障碍对成功治疗房颤至关重要， 开发靶向治疗以预防或减缓认知能力下降。这项试点研究将 为更大的R 01提供数据，以联合收割机成像，PET和Tau生物标志物来检查 AF患者存在多种类型的认知功能障碍。

ABSTRACT Atrial fibrillation (AF) is the most common, costly cardiac arrhythmia affecting over 6 million people in the U.S. with a 2-fold increase in mortality. A major public health problem, AF has serious consequences of stroke and heart failure, and is an independent risk factor for mild cognitive impairment (MCI) and Alzheimer’s-type dementia (AD). Mechanisms of AF-related MCI/AD remain unclear, but possible multifactorial mechanisms include cerebral hypoperfusion, subclinical cerebral ischemia, vascular inflammation, hippocampal brain atrophy, or genetic factors. Improved use of oral anticoagulant (OAC) medications could theoretically reduce subclinical cerebral ischemia, but research on how, or if, OACs effect the rate of progression of cognitive decline has shown conflicting results. While OACs can decrease cerebral ischemia, these drugs increase the risk of cerebral hemorrhage also associated with cognitive decline. There are newer OAC drugs that reduce rates of cerebral ischemia and hemorrhage better than warfarin called non-Vitamin-K inhibitors (NOACs). The goal of the proposed research is to examine the rate of progression of cognitive decline (using neuropsychological and functional testing scores) in patients with AF compared to those without AF in the NIH-sponsored National Alzheimer’s Coordinating Center (NACC) dataset. This longitudinal study with approximately 42,000 community-dwelling adults includes subjects with a range of cognitive impairment (normal, MCI, and dementia). One major methodological problem in prior AF-related MCI/AD studies is inconsistent utilization of the variety of neuropsychological measures that the NACC database includes. We will also compare rate of cognitive decline in AF patients on OAC to those not on OAC and those on NOACs versus warfarin. Additionally, we will explore AD neuropathology (i.e., neurofibrillary tangles), vascular dementia, and mixed AD in AF patients versus those without AF using NACC autopsy data. Women are at higher risk than men of MCI and AD, which is also true of AF-related stroke, indicating significant contribution of sex as a biological variable. The NACC database provides a unique and rich opportunity to examine AF and OAC effects on rate of progression from normal cognition to MCI to AD. Understanding more about AF-related cognitive dysfunction is critical to its successful management and the development of targeted therapies to prevent or slow cognitive decline. This pilot study will provide data for a larger R01 to combine imaging, PET, and Tau biomarkers to examine a variety of types of cognitive impairment in patients with AF.