Cognitive Impairment in Chronic Rhinosinusitis

摘要 认知障碍的特征是记忆、语言、思维或判断方面的问题。 尽管已知认知受损对生活质量和个人健康的巨大影响 健康，除了我们的初步研究；与睡眠时间中断相关的认知功能受损 由于其可能的机制，在炎症性疾病患者中尚未得到客观的研究。 和过敏性呼吸道疾病，如慢性鼻窦炎(CRS)。我们的KL-2支持 研究和初步数据显示，CRS患者存在显著的认知障碍 与与睡眠障碍和睡眠时间变化相关的对照组相比。 利用通过我的KL2获得的经验，这项拟议研究的总体目标是 目的：(1)测定健康对照组和慢性阻塞性肺疾病患者的认知功能特征 上呼吸道炎症；并识别有认知受损风险的人；(2)识别 认知障碍的可预防危险因素包括睡眠时间变化，(3)测试 假设血清IL-6在这一过程中起作用，并可能作为认知的生物标记物 CRS中的损害。 我们已经为我们的试点数据招募了124名个人(69名CRS和55名对照)，并将 计划招募更多研究对象，并完成所有这些病例的数据收集工作 对100名CRS患者和100名对照进行病例对照研究。 目标1将描述认知功能图谱，分析认知功能的6个领域 不同严重程度CRS患者与匹配健康人的病例对照研究 并旨在确定CRS患者认知损害的危险因素。潜在的风险 我们计划研究的因素包括人口统计、社会经济和慢性阻塞性肺病的严重程度；以及 CRS相关合并症(特应性、哮喘等)。 目标2侧重于检验睡眠时间变化与认知功能有关的假设 CRS中的损害。客观测量睡眠时间，包括7天的活动和 昼夜节律评估问卷将在100名以上的CRS和100名对照中进行 病人。进行一系列回归分析的四步统计法 将用于测试CRS严重程度对认知功能的影响是否通过 睡吧。 目的3重点检验血清IL-6是认知障碍的有效生物标志物这一假设 在CRS。为此，将测定血清IL-6水平并将其与认知变量相关联。 患者，使用多变量统计模型。如果发现IL-6具有重要的调节作用， 然后将睡眠变量添加到回归分析中，以探索它们是如何协同工作的 影响IL-6与认知之间的联系。其他炎性细胞因子和可溶性 IL-6受体也将被检测以检验相关假说。

Abstract Cognitive impairment is characterized by problems with memory, language, thinking or judgment. Despite the tremendous known impact of impaired cognition on quality of life and individuals' health, beside our pilot study; impaired cognitive function associated with sleep timing disruption as its potential mechanisms, has not been objectively investigated in patients with inflammatory and allergic respiratory diseases such as Chronic rhinosinusitis (CRS). Our KL-2 supported studies and preliminary data have shown significant cognitive impairment in CRS patients compared to controls that was associated with sleep disturbance and sleep timing changes. Leveraging experienced gained through my KL2, the overall objectives of this proposed study are to: (1) characterize cognitive function profile in both healthy controls and patients with chronic inflammation in upper airways ; and identify those at risk of impaired cognition; (2) identify the preventable risk factors of cognitive impairment including sleep timing shift, (3) test the hypothesis that serum IL-6 has a role in this process and may serve as a biomarker for cognitive impairment in CRS. We have already recruited 124 individuals (69 CRS and 55 controls) for our pilot data and will plan to recruit additional study subjects and complete the data acquisition for all these cases to perform a case control study of 100 CRS patients and 100 controls. Aim 1 will characterize the cognitive function profile analyzing 6 domains of cognitive function in this case-control study of patients with CRS of varied severity compared to matched healthy controls; and also aims to identify risk factors of cognitive impairment in CRS. The potential risk factors we plan to study include demographics, socioeconomic and CRS-severity factors; and CRS-related comorbidities (atopy, asthma, etc.). Aim 2 focuses to test the hypothesis that a sleep-timing shift is linked to cognitive function impairment in CRS. Objective measurements of sleep timing including 7 days actigraphy and circadian rhythm assessment questionnaires will be performed in above 100 CRS and 100 control patients. A four-step statistical approach in which a series of regression analysis are conducted will be applied to test whether the effect of CRS severity on cognitive function is mediated by sleep. Aim 3 focuses to test the hypothesis that serum IL-6 is a valid biomarker for cognitive impairment in CRS. For this aim serum IL-6 level will be determined and related to cognitive variables in patients, using a multi-variate statistical model. If IL-6 is found to have a significant mediation, then sleep variables will be added in the regression analysis to explore how they work together to affect the association between IL-6 and cognition. Other inflammatory cytokines and soluble IL-6 receptor will also be measured to test related hypotheses.