BRAIN CONECTIONS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVES: The three specific aims of this study are 1) to determine the change in continuous measures of cognitive function over time among patients with a recent diagnosis of SLE; 2) to determine the predictive value of neuroimaging for decline in continuous measures of cognitive function in newly diagnosed SLE patients; 3) to determine the predictive value of serologic factors for decline in continuous measures of cognitive function in newly diagnosed SLE patients. METHODS: Thirty patients will undergo a baseline MRI with gadolinium and brain FDG PET, standard neuropsychological testing, disease activity will be assessed by the physician, and a blood sample will be taken. There will be quarterly visits for 3 1/2 to 4 years, depending on entry time. At each visit, the following will be repeated: disease activity measures, serum, plasma, and DNA storage, ANAM, depression inventory, fibromyalgia tender points, AIMS pain scale and ACR NPSLE case definitions. EXPECTED OUTCOME: We hope to find a moderate to severe decline in a clinically relevant number of newly diagnosed SLE patients using continuous measures of cognitive function independent of race, education, socioeconomic status and co-morbid conditions; imaging abnormalities will be more common in cognitively impaired subjects; and abnormalities observed in levels of Antiphospholipid antibodies, cytokines and soluble adhesion molecules will be associated with poorer cognitive function. CLINICAL RELEVANCE: Neuropsychiatric manifestations of Systemic Lupus Erythematosus (NPSLE) are both common and an important source of morbidity. Of the case definitions for NPSLE syndromes that have recently been developed, cognitive dysfunction appears to be the most prevalent. Little is know about the influence of co-morbidities or ethnicity/race on disease outcomes or the underlying pathogenesis of this important NPSLE syndrome. Perhaps most importantly, no rational therapeutic approach for the treatment of SLE-related cognitive dysfunction currently exists and is unlikely to be developed without a better understanding of neuropathological mechanisms. New brain imaging techniques using both structural and functional analyses have the potential to uncover mechanisms underlying NPSLE syndrome, particularly if specific syndromes are targeted.