• Fulvia Ceccarelli, Carmelo Pirone, Concetta Mina, Alfredo Mascolo, Carlo Perricone, Laura Massaro, Francesca Romana Spinelli, Cristiano Alessandri, Guido Valesini, and Fabrizio Conti.
• Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza University of Rome, Rome, Italy.
• Plos One. 2019 Jan 1; 14 (11): e0224437.

BackgroundCognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson's disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far.ObjectivesWe aimed at assessing the PL domain in a Italian monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, the batteria sul linguaggio dell'emisfero destro (BLED). Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features.MethodsForty adult patients affected by SLE, according to the American College of Rheumatology (ACR) criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction.ResultsWe studied 40 Caucasian SLE patients [male (M)/ female (F) 3/37; mean±standard deviation (SD) age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months] and 30 healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 1.3±2.3, mean±SD Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores. As for the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and was significantly more prevalent than memory, executive and visuospatial functions impairment (P = 0.0002, P = 0.0002 and P<0.000001, respectively). According to Global Cognitive Dysfunction score, 25% of patients experienced a mild impairment and 7.5% a moderate one. Anti-phospholipid antibodies positivity was significantly associated with memory impairment (P<0.0005), whereas the presence of other neuropsychiatric events was associated with executive dysfunctions (P<0.05); no further significant association nor correlation were identified.ConclusionIn this study we evaluated for the first time PL in SLE patients finding a dysfunction in almost half of patients. The dysfunction of PL was significantly more frequent than the other domains assessed.

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