Neurocognitive dysfunction in systemic lupus erythematosus: association with antiphospholipid antibodies, disease activity and chronic damage

PLoS One. 2012;7(3):e33824. doi: 10.1371/journal.pone.0033824. Epub 2012 Mar 26.

Abstract

Introduction: Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage.

Methods: Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β(2)-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs).

Results: Nineteen percent of patients had mild GCDs impairment (GCDs 2-3), 7% moderate (GCDs 4-5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = -0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment.

Conclusions: Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Anticardiolipin / blood
  • Antibodies, Anticardiolipin / immunology
  • Antibodies, Antinuclear / blood
  • Antibodies, Antinuclear / immunology
  • Antibodies, Antiphospholipid / blood
  • Antibodies, Antiphospholipid / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Cognition Disorders / blood
  • Cognition Disorders / immunology*
  • Cognition Disorders / physiopathology*
  • Cohort Studies
  • Endothelial Cells / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Logistic Models
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuropsychological Tests
  • Septins / immunology
  • Young Adult

Substances

  • Antibodies, Anticardiolipin
  • Antibodies, Antinuclear
  • Antibodies, Antiphospholipid
  • Autoantibodies
  • Immunoglobulin G
  • SEPTIN2 protein, human
  • Septins