OBJECTIVE: Computerized neuropsychological testing may facilitate screening for cognitive impairment in systemic lupus erythematosus (SLE). This study was undertaken to compare patients with SLE, patients with rheumatoid arthritis (RA), and patients with multiple sclerosis (MS) with healthy controls using the Automated Neuropsychological Assessment Metrics (ANAM). METHODS: Patients with SLE (n = 68), RA (n = 33), and MS (n = 20) were compared with healthy controls (n = 29). Efficiency of cognitive performance on 8 ANAM subtests was examined using throughput (TP), inverse efficiency (IE), and adjusted IE scores. The latter is more sensitive to higher cognitive functions because it adjusts for the impact of simple reaction time on performance. The results were analyzed using O'Brien's generalized least squares test. RESULTS: Control subjects were the most efficient in cognitive performance. MS patients were least efficient overall (as assessed by TP and IE scores) and were less efficient than both SLE patients (P = 0.01) and RA patients (P < 0.01), who did not differ. Adjusted IE scores were similar between SLE patients, RA patients, and controls, reflecting the impact of simple reaction time on cognitive performance. Thus, 50% of SLE patients, 61% of RA patients, and 75% of MS patients had impaired performance on >or=1 ANAM subtest. Only 9% of RA patients and 11% of SLE patients had impaired performance on >or=4 subtests, whereas this was true for 20% of MS patients. CONCLUSION: ANAM is sensitive to cognitive impairment. While such computerized testing may be a valuable screening tool, our results emphasize the lack of specificity of slowed performance as a reliable indicator of impairment of higher cognitive function in SLE patients.