Cognitive Function in SLE (COGNITION)

描述(由申请人提供)：这是一份修订后的申请，用于研究系统性红斑狼疮(SLE)患者与匹配的正常健康对照组的认知功能随时间的变化。我们先前的工作表明，抗磷脂(APL)和抗胸腺P(抗P)抗体的持续存在与SLE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风险因素。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总体上是一致的。在这份申请中，我们建议在3个种族(HA、AA和非西班牙裔白人[n-HW])中登记总共200名SLE受试者，并从德克萨斯大学圣安东尼奥分校(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。我们将测试以下假设：1a-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，调整与认知功能障碍(例如抑郁症、高血压等)相关的非SLE相关并存情况；1b-AA和HA SLE受试者的认知功能将比n-HW SLE受试者更差，调整年龄、教育、SES和与认知功能障碍相关的共病情况(病程、累积的SLE相关损害、疾病活动、药物使用)和没有SLE的人(抑郁症、高血压等)；2a-在SLE患者中，几种生物标志物(APL、抗P和抗谷氨酸受体[抗谷氨酸受体[抗NR2]抗体和基质金属蛋白酶-9[MMP-9]及其组织抑制物[TIMP])的持续阳性水平，在调整了年龄、教育程度、SES和合并症后，将独立地与较差的认知功能相关；2b-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，认知功能障碍将增加。JHMI队列包含相同数量的AA和n-HW SLE受试者，而HSS有HA、AA和n-HW SLE受试者的混合，补充了UTHSCSA的主要HA人群。哥伦比亚大学托管委员会的贝蒂·戴蒙德博士将通过对抗NR2抗体进行抗体检测来合作这一项目。计算机化的神经心理电池(ANAM)将是认知功能的主要衡量标准。可能需要生物标志物和合并症的组合才能导致SLE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认知功能的生物学过程至关重要，这些生物学过程可能有助于逆转疾病的治疗。

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.