Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus

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Web End = Immunol Res (2015) 63:2637 DOI 10.1007/s12026-015-8716-3

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Web End = Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus

Meggan Mackay1

Published online: 19 October 2015 Springer Science+Business Media New York 2015

Abstract Cognitive disturbances, mood disorders and fatigue are common in SLE patients with substantial adverse effects on function and quality of life. Attribution of these clinical ndings to immune-mediated disturbances associated with SLE remains difcult and has compromised research efforts in these areas. Improved understanding of the role of the immune system in neurologic processes essential for cognition including synaptic plasticity, long term potentiation and adult neurogenesis suggests multiple potential mechanisms for altered central nervous system function associated with a chronic inammatory illness such as SLE. This review will focus on the biology of cognition and neuroinammation in normal circumstances and potential biologic mechanisms for cognitive impairment, depression and fatigue attributable to SLE.

Introduction

Neuropsychiatric illness has been associated with systemic lupus erythematosus (SLE) since the systemic manifestations of this disease were rst described by Kaposi in 1872; yet, neuropsychiatric SLE (NPSLE) remains an enigma both clinically and biologically. NPSLE has been classied into 19 syndromes that encompass a wide spectrum of neurologic and psychiatric illness in the peripheral, central, and autonomic nervous systems (Table 1). Attribution of each of these syndromes to an immunologic process directly associated with immune dysregulation in SLE has been extremely difcult as neurologic effects from medications, hormonal and metabolic disturbances, comorbid disease, and infections can be clinically indistinguishable from each other and from SLE. Given the difculties inherent in proposed attribution models where expert opinion remains the gold standard [1, 2], consideration of pathogenic mechanisms contributing to specic syndromes

encompassed by NPSLE is critically important to identify unbiased biomarkers for attribution and the development of diagnostic and therapeutic approaches. This is particularly important for diffuse central nervous system (CNS) NPSLE syndromes where tissue biopsies are not an option, and biologic mechanisms are poorly understood as they are generally not the result of...