Disease Activity and Cognitive Dysfunction
It was previously believed that cognitive function in SLE patients deteriorated irreversibly over time. Recent reports demonstrate changes in cognitive performance that are neither stable nor progressive. Given that SLE fluctuates by nature, several investigators have studied cognitive changes as if they were another manifestation of global disease. In other words, they have evaluated the influence of overall disease activity on cognitive function. Recently, Carlomagno et al. [20*] did not detect any clinically important change in cognitive function over a 1 year period using an instrument designed for use in detecting intellectual damage of a global (ie, non-localized) nature. This held true even in subjects who were cognitively impaired at baseline. Among 17 SLE patients referred for neuropsychological evaluation (ie, cognitive complaints), Skeel et al. describes declines in expressive language, speed of processing and attention compared with estimates of premorbid function; no decline in memory was detected.
Again, the multiplicity of approaches and instruments for assessing both cognition and lupus activity most likely contribute to divergent results. Furthermore, these studies have examined levels of activity at the time of cognitive testing. No doubt other SLE-related issues, such as stress, discomfort or pain, and increased medication (corticosteroids), further confound these results. Gladman et al. [21*] therefore employed a different approach to determine the impact of previous overall and discrete organ system disease activity on current cognitive performance. They developed a multiple regression model to identify predictors of cognitive impairment in SLE patients with no disease activity at the time of testing. Among the various clinical manifestations, only previous vasculitis and higher activity scores at initial presentation (SLEDAI >10) were predictive of cognitive impairment. Neither psychiatric symptoms nor any neurophysiologic tests performed (technetium brain scan, EEG, and QEEG) were associated with impairment. Thus, cognitive dysfunction may be caused by previous disease or its treatment.
These findings suggest that perhaps a consequence specifically inherent to SLE, but generic to SLE flare, may be damaging to the nervous system. Along these lines, Kozora et al. [22**] hypothesized a role for IL-6 (an inflammatory mediator) and various hormones known to be abnormal in SLE in the development of cognitive dysfunction. These hormones include cortisol, dehydroepiandrosteron (DHEA), and DHEA-S (the inactive form). Although IL-6 and cortisol levels did not differentiate SLE patients without neuropsychiatric disease from rheumatoid arthritis patients or healthy controls, DHEA and DHEA-S levels were lower in SLE patients. Lower levels of DHEA and DHEA-S have been reported in different dementia syndromes. Using hierarchical regression modeling to determine the influence of these substances on cognition, IL-6 and DHEA-S were found to account for a unique portion of the variance in measures of learning and attention after controlling for depression and corticosteroid use.
Curr Opin Rheumatol. 2002;14(5) © 2002 Lippincott Williams & Wilkins
Cite this: Cognitive Dysfunction in Neuropsychiatric Systemic Lupus Erythematosus - Medscape - Nov 01, 2002.