Neurocognition and Greater Maintenance of Sinus Rhythm in AF (NOGGIN AF)

房颤是最常见的持续性心律失常，占全身心律失常的1%-3%。 老年人的发病率较高(8%-10%)。房颤与心脏病的风险增加有关 认知衰退、痴呆症、中风、心肌梗塞、心力衰竭、慢性肾脏疾病和死亡率， 导致美国AF每年的增量成本为260亿美元。房颤和认知功能减退有几种风险 因素包括年龄增长和高血压、糖尿病和心力衰竭等并发症。 抗凝、促炎和血栓前状态以及脑低灌注可导致微量出血。 累积导致无症状脑梗塞、脑白质高信号、脑萎缩和脑电活动中断。 功能性网络连通性，也会导致房颤相关的认知功能下降。而房颤和房颤之间的联系 认知功能障碍的发展已经确立，其驱动机制和窦房结效应 节律的恢复还没有完全被理解。 我们的长期目标是了解心率和神经健康之间的相互作用，并 探讨预防房颤所致认知功能障碍的方法。因此，在拟议的研究中，我们将测试我们的 假设在接受口服抗凝的房颤患者中，使用导管恢复窦性心律 消融治疗与药物治疗相比，由于改善了大脑，导致较少的长期神经损伤和功能障碍 血液流动和更低的风险，额外的缺血损伤。我们前瞻性、观察性研究的主要目标 临床试验：1)比较房颤患者阿尔茨海默病高危区域的皮质结构特征 导管消融与药物治疗的比较：2)比较导管治疗的房颤患者的脑血流 消融术与药物治疗房颤患者认知功能的比较 治疗；以及4)评估神经预后与血浆和成像生物标记物之间的关系。 凝血和炎症。这将是第一项包含全面神经认知测试的研究。 电池、结构和功能神经成像、脑血流评估、血浆和成像 A)更好地描述每个已知风险因素对认知发展的贡献 房颤患者的下降，以及b)评估导管消融与药物治疗如何恢复窦性心律 可能会改变认知衰退和痴呆症的发展轨迹。我们的初步数据显示 导管消融术在6周或1年后没有恶化认知功能或脑白质高强度负荷， 而接受药物治疗的患者在1年后表现出更大的皮质变薄，这些区域与 阿尔茨海默氏症，而这种变瘦与认知能力下降有关。因此，这项研究具有重要意义， 将通过以下方式彻底改变我们对房颤机制的理解，从而垂直推进房颤管理领域 哪种房颤会导致认知功能下降，并通过提供重要和必要的步骤来证明节律是正确的 通过导管消融进行控制，作为阻止导致认知障碍和痴呆症的过程的一种策略。

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting 1%-3% of the general population, with greater prevalence in older persons (8%-10%). AF is associated with an increased risk for cognitive decline, dementia, stroke, myocardial infarction, heart failure, chronic kidney disease, and mortality, resulting in an incremental yearly cost of AF in the US of $26 billion. AF and cognitive decline share several risk factors including advancing age and comorbidities such as hypertension, diabetes mellitus, and heart failure. Microbleeds from anticoagulation, a proinflammatory and prothrombotic state, and cerebral hypoperfusion can cumulatively result in silent cerebral infarction, white matter hyperintensities, brain atrophy, and disruption of functional network connectivity, and also lead to AF-related cognitive decline. While the link between AF and the development of cognitive impairment has been established, the driving mechanisms and the effect of sinus rhythm restoration are not completely understood. Our long-term goals are to understand the interaction between heart rhythm and neurologic health, and to investigate methods to prevent cognitive dysfunction due to AF. Thus, in the proposed study, we will test our hypothesis that among AF patients receiving oral anticoagulation, restoration of sinus rhythm with catheter ablation vs drug therapy leads to less long-term neurologic damage and dysfunction due to improved cerebral blood flow and lower risk for additional ischemic injury. The primary aims of our prospective, observational clinical trial are to 1) compare structural cortical characteristics in Alzheimer’s disease-risk regions in AF patients treated with catheter ablation vs drug therapy; 2) compare cerebral blood flow in AF patients treated with catheter ablation vs drug therapy; 3) compare cognitive function in AF patients treated with catheter ablation vs drug therapy; and 4) assess the relationship between neurologic outcomes and plasma and imaging biomarkers of coagulation and inflammation. This will be the first study to incorporate a comprehensive neurocognitive test battery, structural and functional neuroimaging, cerebral blood flow assessment, and plasma and imaging biomarkers to a) better delineate the contribution of each of the known risk factors to the development of cognitive decline in patients with AF, and b) assess how restoration of sinus rhythm using catheter ablation vs drug therapy may alter the trajectory of cognitive decline and development of dementia. Our preliminary data showed that catheter ablation did not worsen cognitive function or white matter hyperintensity burden 6 weeks or 1 year later, while drug therapy patients showed greater cortical thinning at 1 year in brain regions associated with Alzheimer’s, and this thinning correlated with worse cognitive performance. Thus, this study is significant, and will vertically advance the field of AF management by revolutionizing our understanding of the mechanisms by which AF induces cognitive decline, and by providing an important and necessary step toward justifying rhythm control by catheter ablation as a strategy to arrest the processes that lead to cognitive impairment and dementia.