Cognition dysfunction and disease and non-disease associated factors in systemic lupus erythematosus : longitudinal perspectives

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects mostly women of child-bearing age. Neuropsychiatric manifestations of lupus include heterogeneous conditions and are still unknown in the underlying pathogenesis. Cognitive dysfunction is one of the commonest neuropsychiatric manifestations in lupus patients. As cognitive dysfunction in SLE patients may be amenable to prevention and treatment, better understanding of cognitive dysfunction and its associated factors in these patients is important.

In this thesis, some disease- and non-disease related factors contributing to cognitive dysfunction in SLE patients were examined in longitudinal studies. This thesis hypothesized that patients who have past history of cerebral involvement (NPSLE) are more likely to have cognitive dysfunction compared to those without such history, as a result of SLE related pathophysiology. Another hypothesis was that non-disease related factors such as psychiatric symptoms including anxiety and depression predisposes to cognitive symptoms and/or cognitive impairment. Lastly, the usefulness of serum adiponectin, an adipokine that possesses anti-inflammatory activity, as a biomarker of depression in SLE patients was explored. As depression was previously postulated to be related to inflammation and serum adiponectin was reduced in patients with major depression, adiponectin may be a surrogate marker for depression in SLE patients so that these patients can be identified for early intervention.

Firstly, cognitive symptoms were examined by a self-reported questionnaire from a large cohort of SLE patients longitudinally. The results showed that 5.9% of SLE patients had progressive deterioration in 24 months and identified previous NPSLE, bodily pain as disease-related and anxiety and depressive symptoms as non-disease related factors.

Next, full neurocognitive battery for formal evaluation of cognitive function was applied in patients with previous NPSLE. NPSLE patients had worse cognitive function in the domains of simple attention, memory and reasoning after adjustment to confounders compared to SLE patients who did not have such history. NPSLE patients also showed diminished practice effects at reassessment after 12 months. Electrophysiological examination was also performed on NPSLE patients by method of event-related potential P300, which is an index of cognitive function commonly applied in neuroscience research. However, no significant difference in P300 latency or amplitude was found between NPSLE and control SLE patients.

Lastly, depressive symptoms were found to be related to anxiety, pain and fatigue in SLE patients. Serum adiponectin level in SLE patients was measured and lower level was found to be associated with higher depressive symptoms. However, adiponectin level was not found to change significantly when depressive symptoms resolved but correlated with change in SLE disease activity index in longitudinal study.

In conclusion, this thesis showed that past NPSLE was important disease-related factor and represented irreversible factor that predisposed to worse cognitive function by longitudinal study. Anxiety and depressive symptoms were common confounders and important non-disease related factors that contributed to cognitive symptoms and were amendable to treatment. Adiponectin was not shown to be a biomarker for depression in SLE, but was found to be associated with disease activity in longitudinal study and warranted future study.