## 1 Introduction  
Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease of unknown etiology with heterogeneous clinical manifestations, including diverse neuropsychiatric manifestations [1]. SLE affects approximately 1-45.3 per 100,000 people worldwide, with up to 90% of the cases occurring in women of childbearing age [2; 3; 4]. Nervous system disease in SLE includes neurologic and psychiatric events, of which 19%-38% is attributable to SLE [5]. As patients with SLE are living longer, NPSLE has been identified as one of the important factors that hampering the improvement of survival of SLE patients over the past 50 years [6; 7]. NPSLE negatively impacts on health-related quality of life and has been linked to increased unemployment rates [8; 9; 10]. Multiple neuropsychiatric events during the disease course are associated with adverse long-term prognosis with an increased mortality rate of 7%-19% [8]. Clinical manifestations of NPSLE range from overt neurologic or psychiatric dysfunction, such as stroke or psychosis, to more subtle and subclinical abnormalities such as cognitive dysfunction, headache and mood disorders [11]. Around 50%-60% of NPSLE events occur at the onset of SLE or within the first year of diagnosis, commonly in the presence of generalized disease activity [12]. However, it has also become clear that many of the common manifestations of NPSLE are not associated with metrics of diseases, such as flare or severity [6]. NPSLE is difficult to diagnose, secondary factors such as drugs, metabolic abnormalities or infections can contribute to neuropsychiatric disturbances in SLE patients and need to be meticulously excluded [8]. NPSLE is challenging to treat with a lack of controlled randomized trials; the current therapeutic approach to NPSLE remains largely empirical [11]. Thus, there is a need to explore new paradigms for pathophysiologic mechanisms to explain and treat this increasingly important and vexing problem in SLE [6]. Cognition is the sum of intellectual functions resulting in thought and executive function, which comprises reception of external stimuli, information processing, learning, storage and expression [13]. Disturbance of even one of these functions can result in disruption of normal thought [13]. Cognitive dysfunction is a distinct subset of NPSLE and is the most prevalent manifestation of NPSLE [14; 15; 16]. During the 1980s, [PERSON] first established the presence of cognitive dysfunction in SLE patients using formal neuropsychological testing [17; 18]. Cognitive dysfunction has been subsequently reported in 20%-80% of SLE patients, depending on the methodological and diagnostic practices used [19; 20]. Using the one-hour neuropsychological test battery proposed by the American College of Rheumatology in 1999, in various modifications, 15%-80% of SLE patients were diagnosed to have cognitive dysfunction, thus yielding similar results compared to earlier studies [20; 21]. Commonly reported domains of impairment include attention, verbal and visual learning and memory, visuospatial constructional skills, cognitive flexibility, executive functioning and psychomotor speed [22; 23]. Dominant patterns of cognitive deficits have not emerged although the various patterns of impairments suggest a subcortical syndrome reminiscent of white matter dementias [21, 22, 24]. The course of cognitive dysfunction in SLE has been described as evanescent and fluctuating over a 2-5 year period [22, 24]. However, cognitive impairment may be progressive in nature, sometimes reaching the severity of dementia in 3%-5% of lupus patients [12, 22, 23]. Signs of cognitive dysfunction in SLE are often subtle and difficult to ascertain clinically [25]. Relying on patient reporting of cognitive status may not be sufficient given discrepancies between subjective reporting of cognitive difficulties and objective findings on cognitive testing [22].