Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment.

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function.

METHODS: SLE patients aged 18-65 underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data was collected on demographic and clinical variables, disease burden/activity, health related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and chi-square tests.

RESULTS: Of the 238 patients, 90% were female, mean age 41 ± 12 and disease duration 14 ± 10 years at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (p < 0.03) compared with subtype B. Subtype A also, had greater levels of subjective cognitive function (p < 0.001), disease burden/damage (p < 0.04), HRQoL (p < 0.001) and psychiatric measures (p < 0.001) compared with subtype B.

CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multi-factorial phenotypes exist. Those with greater disease burden, from SLE specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately, this will aid our understanding of personalised CI trajectories and identification of appropriate treatments.