This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This study expands the success of a 6 year cohort study of subjects enrolled in 'Clinical and Serologic Predictors of Neuropsychiatric Systemic Lupus Erythematosus .' We explore the neuropsychiatric manifestations of SLE with this project focusing on crucial cognitive aspects. We propose to enroll a total of 200 SLE patients and 200 matched controls from various sites and test the following: Cognitive functioning over time will be worse in the SLE cohort compared to normal controls adjusting for age, ethnicity, education, and co-morbid conditions; Cognitive function will be worse in both AA and MA SLE subjects than in European American SLE subjects adjusting for age, education and co-morbid conditions; Persistently positive levels of antiphospholipid, antiribosomal P and NR2 glutamate receptor antibodies (a new biomarker associated with neuronal apoptosis) will be independently associated with poorer cognitive function. Antibody assays for anti-NR2 glutamate receptor antibodies will be performed. Computerized neuropsychological battery measures cognitive function, its changes, and is its primary measure. To better control for practice effects and increase the ANAM sensitivity, matched non-lupus social network control subjects are enrolled at all sites. It is possible that combinations of autoantibodies and co-morbidities are needed to lead to clinical disease expression, and that these factors are modified by ethnicity. The study information is essential to the successful discovery of biological processes that impact SLE cognitive function and could be potentially amenable to disease-reversing therapies.
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