Cognitive Dysfunction in Atrial Fibrillation

摘要 心房颤动 (AF) 是最常见、费用最高的心律失常，影响超过 600 万人 美国人的死亡率增加了两倍。房颤是一个重大的公共卫生问题 中风和心力衰竭的严重后果，是轻度中风的独立危险因素 认知障碍（MCI）和阿尔茨海默氏型痴呆（AD）。 AF相关机制 MCI/AD 仍不清楚，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。改进口服抗凝药物（OAC）的使用理论上可以减少 亚临床脑缺血，但关于 OAC 如何或是否影响脑缺血进展速度的研究 认知能力下降显示出相互矛盾的结果。虽然 OAC 可以减少脑缺血， 这些药物会增加脑出血的风险，也与认知能力下降有关。 较新的 OAC 药物可以更好地降低脑缺血和出血的发生率 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学方法） 在 NIH 资助的国家研究中，房颤患者与非房颤患者进行比较 阿尔茨海默病协调中心 (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 研究表明，NACC 所采用的各种神经心理学测量方法的使用不一致 数据库包括.我们还将比较接受 OAC 治疗的 AF 患者的认知能力下降率 未服用 OAC 的患者和服用 NOAC 的患者与华法林的比较。此外，我们还将探索 AD AF 患者的神经病理学（即神经原纤维缠结）、血管性痴呆和混合性 AD 使用 NACC 尸检数据与没有 AF 的患者进行比较。女性患 MCI 的风险高于男性 和 AD，这对于 AF 相关的中风也是如此，表明性别作为 生物变量。 NACC 数据库提供了检查 AF 的独特且丰富的机会 OAC 对从正常认知到 MCI 再到 AD 进展速度的影响。理解 有关 AF 相关认知功能障碍的更多信息对其成功管理和治疗至关重要 开发靶向疗法以预防或减缓认知能力下降。这项试点研究将 为更大的 R01 提供数据，以结合成像、PET 和 Tau 生物标记物来检查 AF 患者存在多种类型的认知障碍。

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.