Microstructural Brain Damage Linked to Cognitive Dysfunction and Steroids in Lupus Patients – NUS Study



Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system attacks the body’s own tissues, causing widespread inflammation and damage to affected organs. It can affect the joints, skin, brain, lungs, kidneys and blood vessels. Asian patients with SLE suffer from more severe illness and damage than patients in Western countries.

In Singapore, the prevalence of SLE in children is estimated to be 14.2 per 100,000 children, while that of adult SLE is 40 per 100,000 adults. Cognitive dysfunction is common in patients with SLE. Previous studies have shown that 25% of patients with SLE have cognitive dysfunction, compared to 7.3% in healthy people of the same age and sex. Common cognitive dysfunction demonstrated by patients with SLE includes impaired simple reaction time, sustained and selected attention, memory seeking, working memory, and short-term memory for associations learned, leading to a reduction in health-related quality of life and a negative impact on vocational training. aptitude.

The neural mechanism leading to cognitive dysfunction in patients with SLE remains unknown. Researchers at the NUS Yong Loo Lin School of Medicine attempted to unravel such mechanisms by adopting non-invasive diffusion magnetic resonance imaging (MRI) to study the brains of patients with SLE, especially white matter, coupled computerized neuropsychological assessment. White matter is found under the cortex of gray matter in the human brain and consists of millions of bundles of nerve fibers that transmit signals to different regions of the brain.

Jointly led by Associate Professor Juan Helen Zhou, Center for Sleep and Cognition and Deputy Director of the Center for Translational Magnetic Resonance Research at NUS Medicine, and Associate Professor Anselm Mak, Clinical Researcher in the Division of Rheumatology, Department of Medicine, the group studied the brain’s white matter free water changes in the LED. White matter free water refers to the water molecules surrounding white matter in the brain that are able to diffuse unhindered.

In the article published in Rheumatology, a level 1 journal in the field of rheumatology with Oxford University Press, they compared free water signals in patients with SLE without clinically overt neuropsychiatric manifestations with a group of paired healthy participants using the new free water diffusion. MRI technique. They found that SLE patients had significantly higher amounts of white matter free water than their healthy counterparts, suggesting possible microvascular degradation and / or inflammation. Such increases in free water were significantly related to cognitive dysfunction, particularly sustained attention, as well as a cumulative dose of medical steroids.

“The clinical implications of the study would indicate to physicians that steroids should be prescribed judiciously, aiming for the lowest possible dose for the shortest possible time. While systemic steroid use will continue to be the mainstay of treatment for moderate to severe inflammation associated with SLE, there are other treatment options that could produce similar results: they should be considered first in order to reduce steroid use or shorten the course needed, ”said Assoc Professor Anselm Mak.

He also added that there are other manifestations of SLE that could be treated symptomatically without a prescription for steroids. For example, nonsteroidal anti-inflammatory drugs could be used for milder inflammation, topical treatment for hair loss, and topical pain relievers for mouth ulcers.

Patients with SLE on long-term steroid therapy should also be regularly assessed and monitored for cognitive dysfunction. The researchers noted that the use of the Automated Neuropsychiatric Assessment Matrix (ANAM), which has been validated for use in adult and pediatric patients with SLE, is an effective and efficient tool for these regular assessments.

Further research is needed to determine whether a reduction in the steroid dose is linked to a reduction in white matter free water that leads to improved cognitive function in patients with SLE. The team also wants to further investigate the mechanism of the increase in white matter free water underlying cognitive decline using multimodal imaging, behavioral and blood analyzes in patients with SLE in a longitudinal fashion.

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