This is an application for a Development and Feasibility (D & F) project as part of the MultidisciplinaryClinical Research Center proposal. Systemic lupus erythematosus (SLE) is a disabling autoimmunecondition with multi-organ system involvement. Recently central nervous system (CMS) involvement hasemerged as a major cause of morbidity in SLE. Patients with SLE have an increased risk for cerebrovasculardisease (CVD), and the presence of antiphospholipid antibodies (APLAs) is a recognized risk factor. APLAsare also associated with cognitive dysfunction and markers on magnetic resonance imaging (MRI) studies,even in the absence of other overt neurological signs. Cognitive dysfunction and depression are among themost common manifestations within the neuropsychiatric SLE spectrum. In SLE, etiologies of thesesymptoms remain unclear, although preliminary studies in multiple sclerosis, and extant literature in CVDsuggest that these symptoms are associated with structural changes in frontal brain regions visible by MRIstudies. The proposed study is a cross-sectional investigation of MRI markers, APLA, depression andcognitive dysfunction in SLE.
Aim 1 of this study proposes to evaluate the relationships among depressionand cognitive dysfunction among SLE patients with and without APLAs.
Aim 2 of this investigation proposesto evaluate the contributions of APLA and MRI markers on depression and cognitive dysfunction. DiffusionTensor Imaging (DTI) is an increasingly utilized MRI technology used to detect microscopic structuralchanges in otherwise normal appearing brain matter. Although this technique has proven useful incomparable CNS conditions, this technique has not been studied in SLE. We propose to compare therelative sensitivity of DTI and conventional MRI techniques (T2-weighted MRI) in relation to APLA, cognitivedysfunction and depression. Using this design we may begin to evaluate behavioral and serologicalmarkers, obtainable in the course of clinical care, that identify SLE patients with underlying CNS activity. Inaddition, we may provide preliminary evidence of a model of depression and cognitive dysfunction in SLEprecipitated by underlying frontal CNS changes. This D & F project will provide pilot data and will lay thefoundation for future studies evaluating neuropathological bases of cognitive function and depression in SLE.Such studies may guide the use of preventative interventions for SLE patients at risk for CVD.
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