Cognitive Function in SLE (COGNITION)

描述（由申请人提供）：这是一份修订后的申请，旨在研究系统性红斑狼疮（SLE）患者与匹配组正常健康对照者的认知功能随时间的变化。我们之前的研究表明，抗磷脂（aPL）和抗内糖体P （anti-P）抗体的持续存在与SLE患者的认知功能障碍有关。此外，西班牙裔（HA）种族似乎是认知功能障碍的一个单独的危险因素。这一发现与其他研究中在非裔美国人（AA）和HA SLE患者中观察到的更严重的病程一致。在本申请中，我们建议从3个种族（HA、AA和非西班牙裔白人[n-HW]）中招募200名SLE受试者，并从圣安东尼奥德克萨斯大学HSC （UTHSCSA）、约翰霍普金斯医疗机构（JHMI）和特殊外科医院（HSS）招募200名匹配的对照组。我们将检验以下假设：1、经过与认知功能障碍相关的非SLE合并症（如抑郁症、高血压等）调整后，SLE受试者的认知功能随着时间的推移将比正常对照组更差；根据年龄、受教育程度、社会经济地位以及与SLE患者（病程、SLE相关累积损害、疾病活动性、用药）和非SLE患者（抑郁、高血压等）的认知功能相关的合并症进行调整后，AA型和HA型SLE患者的认知功能均较n-HW型SLE患者差；在调整了年龄、教育程度、社会经济地位和合病条件后，SLE患者持续阳性水平的几种生物标志物（aPL、抗p和抗谷氨酸受体[抗谷氨酸受体[抗inr2]]抗体和基质金属蛋白酶-9 [MMP-9]及其组织抑制剂[TIMP]）将与较差的认知功能独立相关；2b -认知功能障碍在MMP-9/TIMP水平异常且部分或全部自身抗体持续异常的SLE患者中会增加。JHMI队列包含相同数量的AA和n-HW SLE受试者，HSS包含HA、AA和n-HW SLE受试者，补充了UTHSCSA的主要HA人群。哥伦比亚大学董事会的Betty Diamond博士将参与该项目，对抗nr2抗体进行抗体检测。计算机化神经心理电池（ANAM）将是认知功能的主要测量方法。可能需要生物标志物和合并症的组合来导致SLE中认知功能障碍的临床表现，并且这些因素会因种族而改变。从这项研究中获得的信息对于成功发现影响SLE患者认知功能的生物学过程至关重要，这些生物学过程可能潜在地适用于疾病逆转疗法。

DESCRIPTION (provided by applicant): This is a revised application to study cognitive function over time in subjects with Systemic Lupus Erythematosus (SLE) versus a matched group of normal healthy controls. Our prior work demonstrates that the persistent presence of antiphospholipid (aPL), and anti-nbosomal P (anti-P) antibodies are associated with cognitive dysfunction in SLE. Also, Hispanic (HA) ethnicity appears to be a separate risk factor for cognitive dysfunction. This finding is consistent with the more severe disease course overall that has been observed in African American (AA) and HA SLE patients in other studies. In this application we propose to enroll a total of 200 SLE subjects in 3 ethnic groups (HA, AA, and non-Hispanic White [n-HW]) and 200 matched controls from the University of Texas HSC at San Antonio (UTHSCSA), Johns Hopkins Medical Institutions (JHMI) and the Hospital for Special Surgery (HSS). We will test the following Hypotheses: 1a-cognitive functioning over time will be worse in SLE subjects compared to normal controls adjusting for non-SLE related co-morbid conditions associated with cognitive dysfunction (e.g. depression, hypertension, etc.);1b-cognitive function will be worse in both AA and HA SLE subjects compared with n-HW SLE subjects adjusting for age, education, SES, and co-morbid conditions associated with cognitive dysfunction in people with (disease duration, cumulative SLE-related damage, disease activity, medication use) and without SLE (depression, hypertension, etc.); 2a-persistently positive levels of several biomarkers in SLE subjects (aPL, anti-P and anti-glutamate receptor [anti-glutamate receptor [antiNR2] antibodies and matrix metalloproteinase-9 [MMP-9] and its tissue inhibitor [TIMP] will be independently associated with poorer cognitive function after adjusting for age, education, SES, and co-morbid conditions; 2b - cognitive dysfunction will be increased in SLE subjects with abnormal MMP-9/TIMP levels and persistently abnormal levels of some or all of the auto-antibodies. The JHMI Cohort contains equal numbers of AA and n-HW SLE subjects, and HSS has a mixture of HA, AA and n-HW SLE subjects, complementing the primarily HA population at UTHSCSA. Dr. Betty Diamond at The Trustees of Columbia University will collaborate on this project by performing the antibody assays for the anti-NR2 antibodies. A computerized neuropsychological battery (ANAM) will be the primary measure pf cognitive functioning. It is possible that combinations of biomarkers and co-morbidities are needed to lead to the clinical expression of cognitive dysfunction in SLE and that these factors are modified by ethnicity. The information that will be gained from this study is essential for the successful discovery of biological processes that impact on cognitive function in SLE that could be potentially amenable to disease-reversing therapies.