The Impact of Childhood-Onset Lupus on the Developing Brain
Abstract
Systemic lupus erythematosus (lupus) is a chronic autoimmune disease that affects approximately 300, 000 Americans. About 20% of people with lupus have the childhood-onset form, which typically starts in adolescence. Inflammation due to lupus affects multiple organs in the body. It causes organs to function improperly and can sometimes permanently damage them. Lupus that involves the brain is one of the more severe forms of the disease. Brain involvement is more common in the childhood-onset form of lupus, occurring in up to 70% of these patients. This may be because childhood-onset lupus strikes at a critical period of adolescent brain development. Effects of lupus on the brain include cognitive changes, psychiatric changes, seizures, and stroke. Patients with cognitive changes have trouble with attention, focus, memory, and making decisions. They may often complain of “brain fog” due to mental fatigue. Cognitive changes are thought to occur in as many as 60% of patients with childhood-onset lupus, usually within the first year of diagnosis. These changes can have a negative impact on school performance and social interaction, and exert long-term effects. Yet, we face significant challenges in diagnosing and treating young patients with lupus and cognitive involvement. We do not understand why the cognitive changes occur. We do not have accurate tools for diagnosis. We do not have precise treatment. These challenges can lead to delays in diagnosis and treatment, as well as under-treatment or over-treatment of young patients with lupus. This research study seeks to understand how and why childhood-onset lupus affects the developing adolescent brain. The study will look for better ways to identify early cognitive changes, and the factors contributing to the changes. We will use advanced magnetic resonance imaging (MRI) techniques to learn about brain structure and function in adolescents newly diagnosed with lupus. We will study these adolescents over time and compare their brain development to that of healthy peers. The study has three aims: (1) We will compare brain structure, function, and development between adolescents with lupus and healthy peers, using measures obtained by advanced MRI over time. (2) We will look at the relationship between the MRI findings and cognitive test performance. (3) We will look at the relationship between the MRI findings and lupus-related factors, such as disease activity, prednisone exposure, and concurrent depression/anxiety and pain. By examining early cognitive changes in adolescents with lupus, we anticipate that the results of the study will lead to development of better tools for diagnosis and more precise treatment options. The hope is that early treatment can prevent progression to permanent cognitive impairment and improve outcomes for young patients with lupus. This proposed study aligns well with the focus areas of the Department of Defense Lupus Research Program. Focusing on cognitive involvement in childhood-onset lupus will increase our overall understanding of lupus disease mechanisms and heterogeneity, enhancing the ability to subtype patients. Our use of advanced MRI will also advance our understanding of pathobiology of lupus effects on the brain. This knowledge will lead to better approaches for early and accurate diagnosis and for targeted precise treatment of lupus patients. The study is therefore focused on improving the quality of life for individuals living with lupus.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010560
Entities
People
- Andrea Knight
Organizations
- Hospital for Sick Children
- United States Army