Brain Connections

描述(由申请人提供)：系统性红斑狼疮(NPSLE)的神经精神症状是常见的，也是发病率的重要来源。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。关于共病或人种/种族对疾病结果的影响或这种重要的NPSLE综合征的潜在生物学基础，人们知之甚少。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，如果不能更好地了解疾病机制，也不太可能开发出这种方法。新的脑成像技术在揭示NPSLE综合征的潜在机制方面具有巨大的潜力，特别是如果特定的综合征是有针对性的。脑成像和对前瞻性测量的生物标记物的评估也将有助于确定与NPSLE表现相关的因素，并可能有助于区分可逆和不可逆过程。我们建议对100名新诊断的SLE患者进行研究，这些患者来自10个认知功能障碍的发展地点，通过可重复的计算机化和传统的神经心理学测试来确定。我们将前瞻性地评估脑结构和功能成像(使用解剖磁共振成像和静息FDG-PET)、几个相关生物标记物(抗磷脂抗体、细胞因子和黏附分子)以及并存疾病(种族/民族、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。区分暂时性或可逆性认知功能障碍与不可逆性认知功能障碍的因素将使用重复测量分析方法确定。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的关系的能力，对于成功发现可能有助于逆转疾病的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.