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      Intraindividual Change in Cognitive Function Among Adults With Systemic Lupus Erythematosus: A Markov Analysis Over 7 Years

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          Abstract

          Objective

          Cognitive impairment is prevalent in systemic lupus erythematosus (SLE). There remain gaps in understanding cognition and SLE longitudinally. We studied intraindividual change in cognition in SLE over time.

          Methods

          Data were from the University of California, San Francisco Lupus Outcome Study, which included 1281 adults with SLE. The Hopkins Verbal Learning Test‐Revised (HVLT‐R) and the Controlled Oral Word Association Test (COWAT) were administered annually over 7 years. A two‐state Markov analysis was used to model transition intensities for probabilities of change in cognition. Logistic regression examined the association between clinical variables and cognitive change.

          Results

          Minimal transition between cognitive states was observed in the Markov analysis. Using the COWAT, higher levels of self‐reported depression were associated with decreased likelihood of cognitive improvement (Relative Risk [RR]: 0.98; 95% confidence interval [CI]: 0.96‐0.99), and higher self‐reported disease severity was associated with cognitive decline (RR: 1.05; 95% CI: 1.02‐1.09). Using the HVLT‐R, increasing age (RR: 1.02; 95% CI: 1.01‐1.03) and higher education level (RR: 1.82; 95% CI: 1.28‐2.58) were associated with cognitive improvement, and higher self‐reported disease severity (RR: 1.02; 95% CI: 1.01‐1.03) and depression (RR: 1.05; 95% CI: 1.03‐1.07) were associated with cognitive decline.

          Conclusion

          Most individuals with SLE did not transition between states of high (Z score ≥ −1.5) or low (Z score < −1.5) cognition in a Markov analysis over a 7‐year assessment period, highlighting a degree of relative stability in cognition over time. Increasing age and higher education levels were associated with greater likelihood of cognitive improvement. Greater self‐reported SLE disease severity and depression were associated with cognitive decline.

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          Most cited references26

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          The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

          L Radloff (1977)
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            Systemic lupus erythematosus

            Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.
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              The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes.

              To develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE). An international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests. Case definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed. The American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.
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                Author and article information

                Contributors
                zahi.touma@uhn.ca
                Journal
                ACR Open Rheumatol
                ACR Open Rheumatol
                10.1002/(ISSN)2578-5745
                ACR2
                ACR Open Rheumatology
                Wiley Periodicals, Inc. (Boston, USA )
                2578-5745
                27 January 2023
                March 2023
                : 5
                : 3 ( doiID: 10.1002/acr2.v5.3 )
                : 124-131
                Affiliations
                [ 1 ] University of Toronto Toronto Ontario Canada
                [ 2 ] University of Waterloo Waterloo Ontario Canada
                [ 3 ] University of California, San Francisco
                [ 4 ] University Health Network and University of Toronto Toronto Ontario Canada
                Author notes
                [*] [* ] Address correspondence via email to Zahi Touma, MD, PhD, FACP, FACR, at zahi.touma@ 123456uhn.ca .

                Author information
                https://orcid.org/0000-0002-8146-2519
                https://orcid.org/0000-0001-5177-2076
                Article
                ACR211529
                10.1002/acr2.11529
                10010484
                36705542
                a566706a-91b2-4b5f-b346-97acbbaa9c38
                © 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 13 December 2022
                : 13 September 2022
                : 27 December 2022
                Page count
                Figures: 2, Tables: 4, Pages: 8, Words: 6081
                Funding
                Funded by: Lupus Ontario
                Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases , doi 10.13039/100000069;
                Award ID: AR053308
                Funded by: Schroeder Arthritis Institute
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                March 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.6 mode:remove_FC converted:13.03.2023

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