This is an application for a Development and Feasibility (D &F) project as part of the Multidisciplinary Clinical Research Center proposal. Systemic lupus erythematosus (SLE) is a disabling autoimmune condition with multi-organ system involvement. Recently central nervous system (CMS) involvement has emerged as a major cause of morbidity in SLE. Patients with SLE have an increased risk for cerebrovascular disease (CVD), and the presence of antiphospholipid antibodies (APLAs) is a recognized risk factor. APLAs are 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 the most common manifestations within the neuropsychiatric SLE spectrum. In SLE, etiologies of these symptoms remain unclear, although preliminary studies in multiple sclerosis, and extant literature in CVD suggest that these symptoms are associated with structural changes in frontal brain regions visible by MRI studies. The proposed study is a cross-sectional investigation of MRI markers, APLA, depression and cognitive dysfunction in SLE.
Aim 1 of this study proposes to evaluate the relationships among depression and cognitive dysfunction among SLE patients with and without APLAs.
Aim 2 of this investigation proposes to evaluate the contributions of APLA and MRI markers on depression and cognitive dysfunction. Diffusion Tensor Imaging (DTI) is an increasingly utilized MRI technology used to detect microscopic structural changes in otherwise normal appearing brain matter. Although this technique has proven useful in comparable CNS conditions, this technique has not been studied in SLE. We propose to compare the relative sensitivity of DTI and conventional MRI techniques (T2-weighted MRI) in relation to APLA, cognitive dysfunction and depression. Using this design we may begin to evaluate behavioral and serological markers, obtainable in the course of clinical care, that identify SLE patients with underlying CNS activity. In addition, we may provide preliminary evidence of a model of depression and cognitive dysfunction in SLE precipitated by underlying frontal CNS changes. This D &F project will provide pilot data and will lay the foundation 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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