Cardiopulmonary correlates of cognitive function in SLE

描述（由申请人提供）：认知功能障碍常见于系统性红斑狼疮（SLE）等自身免疫性疾病患者。这些缺陷可以影响广泛的活动，更好地了解这些患者的性质和发病机制对于开发有效的治疗方法至关重要。尽管先前有许多研究表明SLE患者与脑功能障碍相关的自身免疫和血管异常，但没有一个特定的潜在机制出现。SLE是一种多器官疾病，高达60%的SLE患者有肺部累及。在一个小样本的SLE受试者中，我们发现了与认知功能障碍相关的意外肺部异常，我们在这项研究中的第一个目的是比较更大的SLE和对照组受试者的肺功能和运动能力，并评估肺功能、运动能力和认知之间的关系。该模型基于先前对慢性阻塞性肺疾病（COPD）患者的研究，其中认知缺陷与肺功能差、运动能力差和抑郁症有关。考虑到SLE表现的异质性，我们将尽量减少某些因素的多样性（如年龄、诊断时间、疾病严重程度和药物使用）。我们还旨在评估和验证简单的自我报告运动测量方法的使用，这种方法易于获得，适用于这一人群，并且有效。这将为未来的研究开发更大规模、更具成本效益的治疗方案。最后，我们的目的是研究运动是否能改善小样本轻度患病的中年SLE患者的认知功能。如果注意到改善，我们将探索其他人群共同的预测因素（即肺功能，运动能力和抑郁）以及自身免疫性SLE疾病特征特有的因素作为变化机制。最终，我们的目标是利用这项试点研究来评估心肺运动作为一种干预措施的可行性和实用性，并指导设计更大规模的试验，以检验这种干预措施在治疗SLE和其他风湿性自身免疫性疾病患者认知功能障碍方面的有效性。

DESCRIPTION (provided by applicant): Cognitive dysfunction is common in patients with autoimmune disorders such as systemic lupus erythematosus (SLE). These deficits can impact a wide range of activities and a better understanding of the nature and pathogenesis is critical to developing effective treatment approaches in these patients. Despite many prior investigations into autoimmune and vascular abnormalities associated with brain dysfunction in SLE, no one specific underlying mechanism has emerged. SLE is a multi-organ disease and pulmonary involvement has been identified in up to 60% of SLE patients. In a small sample of SLE subjects we found unexpected pulmonary abnormalities related to cognitive dysfunction and our first aim in this study is to compare lung function and exercise capacity in a larger cohort of SLE and control subjects, and evaluate the relationship between lung function, exercise capacity and cognition. The model is based on prior studies in patients with chronic obstructive pulmonary disease (COPD) where cognitive deficits have been associated with poor lung function, exercise capacity and depression. Given the heterogeneity of SLE manifestations we will minimize diversity in some factors (i.e. age, length of diagnosis, disease severity and medication use). We also aim to evaluate and validate the use of brief self-report measures of exercise that are easy to obtain, applicable and valid for this population. This will allow development of larger, cost-effective treatment protocols for future investigations. Finally, we aim to examine whether or not exercise improves cognitive function in a small sample of mildly diseased middle aged SLE patients with established disease duration. If improvement is noted we will explore predictors common to other populations (i.e. lung function, exercise capacity and depression) as well as factors specific to autoimmune SLE disease characteristics as mechanisms of change. Ultimately, we aim to use this pilot study to evaluate the feasibility and utility of cardiopulmonary exercise as an intervention and to guide the design of larger trials that will examine the effectiveness of such an intervention in treating cognitive dysfunction in patients with SLE and possibly other rheumatic autoimmune disorders. PUBLIC HEALTH RELEVANCE: Cognitive dysfunction in patients with systemic lupus erythematosus (SLE) is common, and yet mechanisms remain unclear and treatment options limited. This pilot study will investigate basic pulmonary problems and/or exercise limitations contributing to cognitive dysfunction in SLE. It will also examine whether an exercise program for this group is feasible and demonstrates improvement on cognitive ability. Developing novel treatments for cognitive dysfunction in SLE could have positive effects for public health in these and other autoimmune patients.