Cognitive Dysfunction in Atrial Fibrillation

摘要 房颤是最常见、最昂贵的心律失常，影响着600多万人。 美国人的死亡率增加了2倍。作为一个主要的公共卫生问题，AF有 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)和阿尔茨海默型痴呆(AD)。房颤相关机制的研究 MCI/AD尚不清楚，但可能的多因素机制包括脑低灌流， 亚临床脑缺血、血管炎症、海马脑萎缩或遗传 各种因素。改进口服抗凝剂(OAC)药物的使用在理论上可以减少 亚临床脑缺血，但对OAC如何或是否影响进展速度的研究 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， 这些药物增加了脑出血的风险，也与认知能力下降有关。 有较新的OAC药物可以更好地降低脑缺血和出血率 华法林被称为非维生素K抑制剂(NOAC)。拟议研究的目标是 检查认知功能衰退的进展率(使用神经心理学和功能 NIH赞助的国家房颤患者与非房颤患者的测试分数)的比较 阿尔茨海默病协调中心(NACC)数据集。这项纵向研究大约有 42,000名居住在社区的成年人包括有一系列认知障碍的受试者 (正常、MCI和痴呆)。房颤相关MCI/AD的一个主要方法学问题 研究表明，NACC对各种神经心理学措施的利用不一致 数据库包括。我们还将比较接受OAC治疗的房颤患者的认知减退率与 那些没有服用OAC的人，以及那些服用NOAC和华法林的人。此外，我们还将探索AD 房颤患者的神经病理(即神经原纤维缠结)、血管性痴呆和混合性AD 使用NACC尸检数据对比那些没有房颤的人。女性比男性患MCI的风险更高 和AD，这在与房颤相关的中风中也是如此，表明性别作为一种 生物变量。NACC数据库为检查房颤提供了一个独特而丰富的机会 而OAC对从正常认知到MCI再到AD的进展率有影响。理解 更多地了解房颤相关的认知功能障碍对于其成功的治疗和 开发有针对性的治疗方法，以防止或减缓认知能力下降。这项初步研究将 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 房颤患者认知功能障碍类型的多样性。

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.