Cognitive Impairment and Autoantlbodies in Systemic Lupus Erythematosus

Abstract

Nervous system involvement in systemic lupus erythematosus (SLE) includes a wide array of manifestations some of which have been associated with specific autoantibodies. These include reactivity to surface neuronal and lymphocyte antigens, ribosomal P and cardiolipin. The aim of the present study was to examine the association between cognitive abnormalities and these autoantibodies in an unselected female population of SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared to 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Circulating antineuronal antibodies were measured by indirect immunofluorescence using human neuroblastoma cell lines IMR-6 and SK-N-SH. Lymphocytotoxic antibodies were measured by microcytotoxicity. Antibodies to ribosomal P and cardiolipin were measured by ELISA. Antineuronal antibodies were detected in 34%, lymphocytotoxic antibodies in 47%, anti-P antibodies in 17% and anticardiolipin antibodies in 24% of patients. In the cognitively impaired and unimpaired SLE patients there was no significant difference in the prevalence of antineuronal antibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%), anti-P antibodies (20 vs 17%) or anticardiolipin antibodies (7 vs 29%). The titre and isotype of autoantibodies were also similar in both groups. These results suggest that autoantibodies which have previously been associated with nervous system manifestations of SLE are not likely to be directly involved in the pathogenesis of cognitive dysfunction.

Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: An international inception cohort study

“…However, these prevalence rates fell to 24% and 4%, respectively, when mild cognitive impairment was excluded. This decision rule for cognitive impairment in SLE patients is similar to that used in a previous study (17), with comparable findings for the prevalence of cognitive impairment in SLE patients and controls. A sensitivity analysis performed in the current study assessing all 19 NP syndromes indicated the profound effect, in terms of frequency, of the use of different decision rules for timing of the onset of the NP event and identifying alternative diagnoses.…”

Cognitive function in systemic lupus erythematosus: Results of a 5‐year prospective study

“…Cross-sectional studies (1-6) have defined the characteristics of cognitive dysfunction and its prevalence, which has varied from 21% to 66% due t o differences in study populations, the particular neuropsychological tests used, and the definition of cognitive impairment. Most studies have identified subclinical cognitive dysfunction in a substantial proportion of patients (1)(2)(3)(4). It is important to know whether these abnormalities in cognitive function progress over time to more profound cognitive dysfunction or whether they signal the eventual emergence of other clinically overt manifestations of neuropsychiatric SLE (NPSLE).…”

“…In 1989-1990,70 consecutive SLE patients underwent neuropsychological assessment (2). After a 12-month interval, 59 patients had a repeat assessment (7), and 60 months from the time of the initial assessment, 53 patients were reevaluated.…”

“…This test battery is focused primarily on verbal learning. Decision rules for cognitive impairment have been described previously (2). To determine the functional significance of cognitive impairment, 2 validated, self-administered quality-of-life questionnaires were used at the final assessment, i.e., the Medical Outcomes Survey Short Form-36 (SF-36) (11) and the Sickness Impact Profile (SIP) (12).…”

“…Changes in neuropsychological test performance over the 5-year period of study were examined by 2-way repeated-measures analysis of variance (ANOVA). Time was the within-subjects factor, and a separate analysis was conducted for each of the following between-subjects factors: clinically overt NPSLE at any time in the disease course, presence or absence of corticosteroid treatment at the time of each assessment (with those patients who alternated between taking and not taking corticosteroids forming a third group), and presence of cognitive impairment at the initial assessment (as determined by the previously described decision rules) (2). Separate analyses were conducted for each of the following response variables: information, similarities, picture completion, block design, and digit symbol subtests of the WAS-R; digit span forward, digit span backward, visual memory span forward, and visual memory span backward of the WMS-R; and list A trials 1-5, list A trial 1, List A trial 5, long-delay free recall, and discriminability (i.e., recognition memory) of the CVLT.…”