Managing Cognitive Dysfunction in Systemic Lupus Erythematosus

Cognitive dysfunction, including impairments in attention, recall, concentration, information processing speed, spatial processing, and word finding, is a frequent occurrence in patients with systemic lupus erythematosus (SLE).^1,2 With severity ranging from mild impairment to severe dementia, cognitive dysfunction in patients with SLE is associated with substantial negative effects on functioning, employment potential, and quality of life.³ The pathogenic pathways of SLE-related cognitive dysfunction are yet to be fully elucidated, but vasculopathy, antibody-mediated neurotoxicity, impairments in cytokine signaling, and complement abnormalities have all been proposed as contributing factors.^4–6 Because of different definitions and criteria, inconsistent modes of assessment, and difficulty in ascertaining which cases of cognitive impairment should be attributed to the SLE disease process, the prevalence of SLE-related cognitive dysfunction has been difficult to ascertain. Current estimates range from 21% to 80%.⁴

Zahi Touma, MD, PhD, FACP, FACR, from the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, and University of Toronto Lupus Clinic, is coauthor of a recent systematic review and meta-analysis that examined the prevalence of cognitive dysfunction in patients with CLE.⁷ In an interview with Rheumatology Advisor, Dr Touma explained how rheumatologists can address the challenge of cognitive dysfunction in their patients with SLE.

Rheumatology Advisor: What are the effects of cognitive dysfunction on patients with SLE?

Dr Touma: The nervous system is commonly affected by SLE; the American College of Rheumatology has described 19 manifestations defined as neuropsychiatric SLE (NPSLE). Cognitive impairment (CI) is 1 of the most common manifestations of NPSLE, and can happen at any time in the course of the disease. In our recent systematic review of the literature, the pooled prevalence of CI was 38% (95% CI, 33%-43%). We also found that [patients with lupus] have a higher relative risk of developing CI compared with patients with rheumatoid arthritis and with healthy individuals (relative risk, 1.80 and 2.80, respectively). Patients with SLE often report cognitive problems (attention/vigilance, visuospatial span of attention/working memory, and simple reaction time). However, the diagnosis of CI is very challenging and often delayed, and, more importantly, its monitoring is inconsistent. Studies have shown that CI can negatively affect patients’ quality of life. Also, CI can have a negative effect on employment. However, little is known about specific daily life activity and social role participation in patients with CI. Dr Lisa Engel, a postdoctoral research fellow in my lab, is currently conducting several research projects to evaluate the effects of CI on patients’ everyday life activity limitations and life role participation restrictions.

Rheumatology Advisor: Should rheumatologists routinely monitor patients with SLE for cognitive dysfunction?

Dr Touma: The answer is yes. Early detection of CI is essential to direct patient care so as to help patients adapt accordingly to lessen the effects of possible cognitive decline and disability. However, as mentioned here, the screening, diagnosis, and monitoring for CI in lupus is not well developed. The gold standard test recommended by the American College of Rheumatology to assess cognitive function is a 1- to 2-hour battery (American College of Rheumatology-SLE battery) of tests.⁷ These tests are administered and scored by psychometrists and interpreted by neuropsychologists. Unfortunately, the application of this battery is time consuming and is associated with a cost burden. Further studies are needed to determine the best screening and diagnostic tests for CI in lupus while considering the cost and the administration burden on the patients and the caregivers. Several studies have looked into the association between objective CI (measured by cognitive battery) and subjective CI (self-report measure completed by the patients). The results of the studies showed that subjective CI is often associated with underlying depression and/or anxiety. Other studies showed discrepancies between subjective and objective CI. Nevertheless, subjective CI should be measured because the perceived deficits by the patients can be functionally disabling. [Patients with lupus] should be routinely assessed for depression and anxiety.

Rheumatology Advisor: What treatments are available to address cognitive dysfunction in patients with SLE?

Dr Touma: Currently, there is no specific treatment for CI in lupus. It is still to be determined whether a better control of lupus disease activity will have an influence on CI development and trajectory over time. Future studies should assess the role of psychoeducational intervention programs to improve the outcomes of patients with CI. Several studies found an association between CI and depression; thus, patients with CI should be routinely screened for depression and treated adequately. Also, several studies highlighted the role of education as a protective factor against CI development; therefore, more childhood education might be beneficial.

Rheumatology Advisor: What else should rheumatologists know about cognitive dysfunction in patients with SLE?

Dr Touma: We hope that future research will identify the best screening and diagnostic tests for CI. In addition, ongoing research on cognitive function with advanced brain magnetic resonance imaging techniques should shed a light on CI phenotypes, etiology/pathogenesis, and course over time. Measuring and quantifying CI adequately will enhance the development of preventive and therapeutic strategies.

Dr Touma’s research is supported by the Arthritis Society and the Physicians’ Services Incorporated Foundation.

References

1. Benedict RHB, Shucard JL, Zivadinov R, Shucard DW. Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis. Neuropsychol Rev. 2008;18(2):149-166.
2. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42(4):599-608.
3. Nantes SG, Su J, Dhaliwal A, Colosimo K, Touma Z. Performance of screening tests for cognitive impairment in systemic lupus erythematosus. J Rheumatol. 2017;44(11):1583-1589.
4. Mackay M. Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus. Immunol Res. 2015;63(1-3):26-37.
5. Kivity S, Agmon-Levin N, Zandman-Goddard G, Chapman J, Shoenfeld Y. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med. 2015;13(1):43.
6. Magro-Checa C, Schaarenburg RA, Beaart HJL, Huizinga TWJ, Steup-Beekman GM, Trouw LA. Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus. Lupus. 2016;25(8):878-888.
7. Rayes HA, Tani C, Kwan A, et al. What is the prevalence of cognitive impairment in lupus and which instruments are used to measure it? A systematic review and meta-analysis [published online February 20, 2018]. Semin Arthritis Rheum. doi: 10.1016/j.semarthrit.2018.02.007