Researchers Report Two Predictors of Neuropsychological Dysfunction in Lupus Patients

Researchers at The Feinstein Institute for Medical Research in Manhasset, New York recently published in the journal Lupus Science & Medicine their finding on two predictors of neuropsychological dysfunction in individuals with systemic lupus erythematosus (SLE). The study is entitled “Brain metabolism and autoantibody titres predict functional impairment in systemic lupus erythematosus.”

SLE is a severe autoimmune disease in which the body’s own immune system overreacts and attacks healthy joints and organs, resulting in inflammation, swelling, pain, disability and often in tissue destruction. Cognitive impairment and behavioral disturbances such as anxiety and mood disorders are often observed in neuropsychiatric systemic lupus erythematosus (NPSLE) patients.

DNRAbs is a subset of anti-double stranded DNA auto-antibodies that cross-react with N-methyl d-aspartate receptors (NMDARs) on neurons. The concentration of DNRAbs was previously found to determine neuronal activation, dysfunction or death, and a correlation has been reported between high titres of antibody and severe manifestations of NPSLE, like seizures, mood and anxiety disorders, acute confusional state, psychosis and cognitive dysfunction.

In this study, the possible relationship between SLE duration or serology (serum DNRAbs titers) with abnormal brain glucose metabolism and deficits on neuropsychological testing (cognitive and behavioral performance) in SLE patients was assessed. [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) was used to determine the metabolic activity of brain tissue by the level of glucose uptake. Previous studies with FDG-PET had demonstrated that patients with prolonged SLE disease exhibited a reduced metabolism in certain brain regions, predicting further clinical deterioration.

Patients with stable SLE disease activity, with no signs of brain damage or symptoms of NPSLE were grouped according to disease duration into short-term (ST-SLE; disease for 2 years or less) and long-term (LT-SLE; disease for more than 10 years). All patients were submitted to clinical evaluation, neuropsychological tests, resting FDG-PET scan imaging and measurement of DNRAb serum titers.

Researchers found that patients with LT-SLE exhibited hypometabolism (low or slow metabolic rate) on FDG-PET scans, namely in the prefrontal and premotor brain cortices. This correlated with increased SLE-related damage, but not with DNRAb titer or neuropsychological performance. Interestingly, both patient groups independently of disease duration, exhibited hypermetabolism in the hippocampus and orbitofrontal cortex that was linked to impaired memory performance and mood alterations. Serum DNRAb was also found to be associated to impaired memory performance and increased anxiety.

The research team concluded that both the presence of DNRAbs in the serum and increased hippocampal metabolism could be used as independent predictors of poor cognitive and behavioral performance in SLE patients, irrespective of disease duration. The combination of these two markers improves the accuracy of the prediction.