Brain Connections

描述（由申请人提供）：系统性红斑狼疮（NPSLE）的神经精神表现是常见的，也是发病的重要来源。在最近开发的NPSLE综合征的病例定义中，认知功能障碍似乎是最普遍的。关于共病或种族/人种对疾病结局的影响或这种重要的NPSLE综合征的潜在生物学基础知之甚少。也许最重要的是，目前还没有合理的治疗方法来治疗SLE相关的认知功能障碍，如果不更好地了解疾病机制，就不太可能开发出这种治疗方法。新的脑成像技术有很大的潜力，揭示NPSLE综合征的机制，特别是如果特定的综合征为目标。脑成像和前瞻性测量的生物标志物的评价也将有助于确定与NPSLE表现相关的因素，并可能有助于区分可逆性和不可逆性过程。我们建议研究100例新诊断的SLE患者从10个站点的认知功能障碍的发展，确定使用可重复的计算机和传统的神经心理学测试。我们将前瞻性评价结构和功能性脑成像（使用解剖磁共振成像和静息FDG-PET）、几种相关生物标志物（抗磷脂抗体、细胞因子和粘附分子）和共病（人种/种族、抑郁症、纤维肌痛和皮质类固醇使用）与认知功能障碍的关系。我们还将确定认知功能障碍对生活质量的影响。将使用重复测量分析方法确定区分短暂或可逆与不可逆认知功能障碍的因素。在一组新诊断的SLE患者中，研究认知功能变化与这些其他变量之间关系的能力对于成功发现可能适用于疾病逆转治疗的早期病理变化至关重要。

DESCRIPTION (provided by applicant): Neuropsychiatric manifestations of Systemic Lupus Erythematosus (NPSLE) are both common and an important source of morbidity. Of the case definitions for NPSLE syndromes that have recently been developed, cognitive dysfunction appears to be the most prevalent. Little is known about the influence of co-morbidities or ethnicity/race on disease outcomes or the underlying biological basis for this important NPSLE syndrome. Perhaps most importantly, no rational therapeutic approach for the treatment of SLE-related cognitive dysfunction currently exists and is unlikely to be developed without a better understanding of disease mechanisms. New brain imaging techniques have great potential to uncover mechanisms underlying NPSLE syndromes, particularly if specific syndromes are targeted. Brain imaging and the evaluation of prospectively measured biomarkers will also help determine factors that are relevant to NPSLE manifestations and may help distinguish reversible from irreversible processes. We propose to study 100 newly diagnosed patients with SLE from 10 sites for the development of cognitive dysfunction, determined using both repeatable computerized and traditional neuropsychological tests. We will prospectively evaluate the relationship of structural and functional brain imaging (using anatomic magnetic resonance imaging and resting FDG-PET), several relevant biomarkers (antiphospholipid antibodies, cytokines and adhesion molecules) and co-morbidities (race/ethnicity, depression, fibromyalgia and corticosteroid use) to cognitive dysfunction. We will also determine the impact of cognitive dysfunction on quality of life. Factors distinguishing transient or reversible versus irreversible cognitive dysfunction will be determined using a repeated measures analysis approach. The ability to study the relationship between changes in cognitive functioning and these other variables in a group of newly diagnosed SLE patients is crucial to the successful discovery of early pathologic changes that could be potentially amenable to disease-reversing therapies.