Cognitive Dysfunction in Neuropsychiatric Systemic Lupus Erythematosus

Melanie J. Harrison, MD, MS, Lisa D. Ravdin, PhD


Curr Opin Rheumatol. 2002;14(5) 

In This Article

Influence of Neuropsychiatric Disease and Emotional Disturbances

Depression and anxiety are common complaints of SLE patients, the etiology of which may be a direct manifestation of CNS involvement or a secondary response to a life-altering chronic illness. Mood and psychological factors are known to influence reports of cognitive functioning as well as performance on neuropsychological tests.[14] The high prevalence of psychological distress in this population has led some to argue that cognitive deficits can be attributed to the psychological factors of living with a chronic disease.[15] However, high self-ratings of depressive symptoms have been found in SLE patients compared with other chronic disease populations. Kozora et al.[16] found increased self-ratings of depression in their sample of SLE patients without neuropsychiatric symptoms compared with rheumatoid arthritis patients and healthy controls. Significant associations were observed between the somatic symptoms of depression and a cognitive domain score for learning based on performance on memory measures; there was no relation between the cognitive aspects of depression and neuropsychological test performance.

Longitudinal data suggest that SLE patients with psychiatric involvement experience an improvement in cognition with improved psychiatric status at 1-year follow-up that is not observed in patients with persisting psychiatric disorders[5] However, the degree of emotional disturbance in SLE patients does not always correlate with observed cognitive dysfunction or disease activity[17] Further, cognitive dysfunction has been documented in SLE patients in the absence of measurable psychological distress. More recently, Segui et al.[18] recruited 20 consecutive SLE patients to longitudinally investigate psychiatric status when presenting with a flare and then again at 1 year follow-up. They did not find any significant differences when comparing cognition, depression, and ratings of physical disability between the initial (active) presentation and while inactive at 1-year follow-up. These authors concluded that psychiatric distress during acute episodes reflects the psychological impact of disease activity, and are analogous to the response exhibited by other patient groups suffering a stressful event.

Many SLE patients present with more than one neuropsychiatric manifestation of disease (ie, the categories are not mutually exclusive). In fact, cognitive dysfunction itself may be related to, if not caused by, many of the others specified in the Nomenclature (ie, cerebrovascular accident, depression). Recently, Monastero et al.[19] found cognitive impairment in SLE patients with and without overt neuropsychiatric manifestations of disease compared with age-matched healthy controls. In this investigation, 75 women with SLE underwent a comprehensive battery of neuropsychological tests as well as clinician's ratings of depression and anxiety (Hamilton Rating Scales). Results revealed compromised performance on tests of verbal learning and recall as well as reproduction and recall of a complex figure. Post hoc analyses showed that the neuropsychiatric SLE patients performed more poorly than SLE patients without neuropsychiatric involvement, and both patient groups performed worse than the controls. However, only the neuropsychiatric SLE patients differed significantly from the controls on measures of depression and anxiety. The authors report that multivariate analyses found that depression was the only clinical variable that predicted cognitive test performance. Closer analysis of the data reveals that despite the statistically significant differences in psychological symptoms, the group means on the Hamilton scales were not clinically significant. Thus, although the neuropsychiatric SLE group reported a greater number of symptoms consistent with depression, they were not clinically depressed. Therefore, it is unlikely that the dysphoria experienced by these patients could account for their cognitive deficits. Perhaps greater depressive symptoms in neuropsychiatric SLE patients relative to SLE patients without neuropsychiatric involvement is a gross measure of CNS disease, rather than psychological distress.


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