Patterns and prevalence of cognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which cognitive dysfunction is common, but poorly understood. This study aims to characterize the prevalence and patterns of cognitive dysfunction in SLE. METHOD: SLE patients (n = 95) and demographically matched healthy controls (n = 48) underwent cross-sectional cognitive testing using the 1-hr conventional neuropsychological test battery recommended by the American College of Rheumatology for use in SLE. We used standard deviations (SD) from the healthy control group to define impairment. For each cognitive test we compared SLE and control groups using independent samples t-tests (or alternatives when needed). We performed cluster analysis using a machine learning algorithm to look for patterns of cognitive dysfunction. RESULTS: The SLE group performed significantly worse than healthy controls on every cognitive test. The largest differences were in the domains of verbal fluency, working memory and attention, while fine motor and psychomotor speed were the least affected domains. As expected, the prevalence of cognitive dysfunction varied depending on the SD cut-off used, with 49% of participants being >1.5 SD below the healthy control mean in at least two cognitive domains. Heat mapping showed variability in the pattern of dysfunction between individual patients and cluster analysis confirmed the presence of two clusters of patients, which were those significantly impaired versus those having preserved cognition. CONCLUSIONS: Cognitive dysfunction is common in SLE but markedly heterogeneous across both cognitive domains and across the SLE group. Cluster analysis supports the use of a binary definition of cognitive dysfunction in SLE.

Clinical associations of cognitive dysfunction in systemic lupus erythematosus.

OBJECTIVE: Cognitive dysfunction in SLE is common, but clinical risk factors are poorly understood. This study aims to explore the associations of cognitive dysfunction in SLE with disease activity, organ damage, biomarkers and medications. METHODS: We performed cross-sectional cognitive assessment using a conventional neuropsychological test battery, with normative values derived from demographically matched healthy subjects. Endpoints included two binary definitions of cognitive dysfunction and seven individual cognitive domain scores. Clinical parameters included disease activity (SLEDAI-2K) and organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We performed regression analyses to determine associations between clinical parameters and cognitive endpoints. RESULTS: 89 patients with SLE were studied, with median age of 45 and disease duration of 15 years. Organ damage was significantly associated with severe cognitive dysfunction (OR 1.49, CI 1.01-2.22) and worse cognitive test performance in three of the seven individual cognitive domains. In contrast, no significant associations were found between SLEDAI-2K at the time of cognitive assessment and any cognitive endpoints on multivariate analysis. Higher time-adjusted mean SLEDAI-2K was associated with better verbal memory scores but had no significant associations with other cognitive endpoints. The presence of anti-dsDNA antibodies and high IFN gene signature were negatively associated with severe cognitive dysfunction; there were no significant associations with the other autoantibodies studied or any medications. Substance use was significantly associated with lower psychomotor speed. Only 8% of patients who had cognitive dysfunction on testing had been recognised by clinicians on their SDI score. CONCLUSIONS: In SLE, cognitive dysfunction was positively associated with organ damage, but not associated with disease activity, and serological activity and high IFN signature were negatively associated. Cognitive dysfunction was poorly captured by clinicians. These findings have implications for preventative strategies addressing cognitive dysfunction in SLE.

Fibromyalgia, mood disorders, cognitive test results, cognitive symptoms and quality of life in systemic lupus erythematosus.

OBJECTIVES: Cognitive dysfunction, and comorbidities such as mood disorder and fibromyalgia, are common in SLE. This study aims to explore the associations between fibromyalgia, mood disorders, cognitive symptoms and cognitive dysfunction in SLE patients, and their impact on quality of life. METHODS: We tested cognition in SLE patients and healthy controls, and evaluated cognitive symptoms, mood disorder, fibromyalgia, fatigue and quality of life using patient-reported outcome measures. We examined associations of these comorbidities with both patient-reported cognitive symptoms and cognitive test performance. RESULTS: High fibromyalgia symptom score and history of depression or anxiety were associated with cognitive dysfunction. There were no significant associations between current depression, anxiety symptoms or fatigue score and objective cognitive dysfunction. In contrast, mood disorder symptoms, history of mood disorder, fibromyalgia symptoms and fatigue all had significant associations with patient-reported cognitive symptoms. There were no significant associations between patient-reported cognitive symptoms and objective cognitive dysfunction. Objective cognitive dysfunction, patient-reported cognitive symptoms, history of mood disorder and fibromyalgia symptoms all had significant associations with poorer quality of life; fibromyalgia had the biggest impact. CONCLUSIONS: Cognitive symptoms are common in SLE, but there were no associations between cognitive symptoms and objective cognitive dysfunction. Depression, anxiety and fibromyalgia were more consistently associated with patient-reported cognitive symptoms than with objective cognitive dysfunction. These factors all have a significant impact on quality of life. Understanding the discrepancy between patient-reported cognitive symptoms and cognitive test performance is essential to advance care in this area of unmet need.

Cognitive dysfunction in systemic lupus erythematosus: how do we advance our understanding?

Despite the high reported prevalence and burden of cognitive dysfunction in systemic lupus erythematosus (SLE), there is poor understanding of its aetiology, clinical assessment, and management. In part, this lack of understanding is due to conceptual disorganisation in the available literature. In this Review, we address key knowledge gaps in the nomenclature, assessment, and interpretation of cognitive dysfunction in SLE. We apply basic principles of neuropsychology and incorporate lessons from other disease states to recommend principles that can help researchers to design studies in SLE. Better understanding of the trajectory of cognitive dysfunction in SLE will help to inform therapeutic trials, including the appropriate selection of outcome measures to capture clinically meaningful responses.

Evaluation of the Montreal Cognitive Assessment as a screening tool for cognitive dysfunction in SLE.

OBJECTIVES: Cognitive dysfunction in SLE is common and associated with significant morbidity but is currently underdetected. Early detection requires the use of screening tests, as formal diagnostic cognitive testing is time-consuming. This study aims to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in SLE. METHODS: Patients with SLE (n=95) and demographically matched healthy control participants (n=48) underwent cognitive testing using the 1-hour neuropsychiatric test battery recommended by the American College of Rheumatology for use in SLE and the MoCA. We used regression analyses to determine associations between MoCA and cognitive test scores. We assessed several MoCA cut-offs for predicting cognitive impairment in terms of sensitivity, specificity, positive predictive value and negative predictive value. Receiver operating curve analyses were used to determine the diagnostic accuracy of the MoCA cut-off thresholds. RESULTS: We found a significant correlation between MoCA score and 9 of the 10 cognitive endpoints studied (all p<0.001). Receiver operating curve analysis suggested that a MoCA cut-off of <27 had highest diagnostic accuracy across the cognitive impairment definitions (area under the curve 0.76-0.78). Using a screening cut-off of <28, the MoCA had sensitivity of 83%-94% and specificity of 46%-59%, depending on the impairment definition used. CONCLUSIONS: The MoCA correlates strongly with cognitive test results in SLE and has sufficient sensitivity for use as a screening tool with a cut-off of <28 as the optimal threshold. This tool can be incorporated into clinical practice for screening for cognitive dysfunction in SLE.

Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis.

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.

Qualitative assessment of medication adherence in patients with rheumatic diseases on biologic therapy.

INTRODUCTION/OBJECTIVES: Despite close management in specialized clinics, medication adherence remains a significant problem for some patients. The study aims to explore factors affecting medication adherence in patients attending a biologics clinic. METHOD: Participants completed surveys including the Compliance Questionnaire Rheumatology (CQR) to quantify adherence rates. Purposive sampling targeting poorly adherent patients was used to select individuals for qualitative evaluation. Semi-structured interviews were performed and continued until saturation was achieved. Interviews were transcribed and coded using NVivo. Principles of grounded theory were used for data analysis. RESULTS: A total of 123 patients completed the survey (72 RA, 33 PsA, 18 AS). Of which, 96 patients completed all CQR items, of these 72% were identified as adequately adherent. A major theme which emerged from patient interviews was that the presence of active symptoms significantly influenced adherence. Patients tended not to prioritize medication taking until they had a recurrence of symptoms. Despite describing biologics as "life-changing", patients expressed concern regarding potential long-term side effects of these medications which affected adherence. Patients identified their relationship with their rheumatologist as pivotal and perceived diet, exercise and stress as critical. Intentional factors were the predominant drivers for non-adherence; patients made a risk-benefit analysis based on their beliefs and chose to not take their medications as prescribed. CONCLUSIONS: Medication adherence to traditional and biological therapies was lower than expected by treating clinicians in this patient group, who are closely supported in a dedicated biologics clinic. Several of the identified themes suggest that shared decision making and enhancing patient education may improve adherence in this group. Key Points • Adherence rates are suboptimal even in supported, educated, English-speaking patients in the biologics era. • Contributing factors were 'intentional' as patients chose to be non-adherent based on their beliefs. • Emergent themes suggest that enhancing patient education could improve adherence.

Independent association of glucocorticoids with damage accrual in SLE.

OBJECTIVES: To determine factors associated with damage accrual in a prospective cohort of patients with SLE. METHODS: Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. RESULTS: A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI. CONCLUSIONS: Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.