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Functional performance in patients with SLE linked to presence of DNRAbs
The presence of antibody to N-methyl-D-aspartate receptor in serum titers and resting brain hypermetabolism were linked to impaired memory function and mood alterations in patients with systemic lupus erythematosus, researchers found.
Serum titers of antibody to N-methyl-D-aspartate receptor (DNRAb) and [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) were explored in nine patients with short-term (disease duration of 2 years or less) systemic lupus erythematosus (SLE) and in eight patients with long-term (more than 10 years) SLE. Seventeen healthy control participants were also recruited.
Patients with SLE were assessed within 2 weeks of FDG-PET imaging using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics Damage Index (SLICCDI), and cognitive function was evaluated on the day of imaging with the Automated Neuropsychological Assessment Metric (ANAM). The Beck Depression Inventory (BDI) was administered, along with the State-Trait Anxiety Inventory and mood assessment domains included in the ANAM. Blood was collected for serum analysis of DNRAb and standard markers of SLE disease activity.
All patients with SLE and healthy participants underwent FDG-PET imaging after an overnight fast. Thirty-five minutes after the injection of 3.5 mCi FDG, autoradiographic PET images were acquired in a dimly lit room with minimal auditory stimulation over a 20-minute period.
A voxel-wise search of whole brain volume was conducted using the two-sample t-test option to evaluate and compare regional metabolic activity between the three groups of participants. Spherical volumes of interest (VOIs) centered at the peak volume of each cluster were used to identify metabolic activity in specific brain regions.
Use of prednisone or disease-modifying drugs, serum markers for disease activity, SLEDAI and SLICCDI scores did not correlate with ANAM scores, but scores between short-term and long-term patients with SLE were similar, according to the researchers.
Compared with healthy participants, significantly increased brain metabolism was seen in both SLE groups based on a voxel-by-voxel whole-brain volume search, particularly in the hippocampus, orbitofrontal cortex (Brodmann area), posterior putamen and globus pallidus. No differences were seen between the two groups of patients with SLE.
Significant reductions were seen in metabolic activity in the prefrontal and premotor regions in long-term patients with SLE compared with patients with short-term SLE and with the healthy participants.
Based on ANAM results, correlations with the running memory continuous performance test were seen with metabolism in the left hippocampus, and impaired function seen in the code substitution and memory search tests was associated with metabolic activity in the orbitofrontal cortex, according to the researchers. Sustained attention was correlated with left orbitofrontal hypermetabolism. In the right orbitofrontal region, performance with math processing was inversely associated with metabolic activity. Increasing right hippocampal activity correlated with scores for depression. No correlations were observed between metabolism in the basal ganglia and cognitive or behavioral performance.
Total throughput scores for ANAM subtests were inversely correlated with DNRAb serum titer levels. Increased metabolic activity in the left hippocampus and orbitofrontal region, poor memory performance and depression were associated with increased DNRAb.
Left hippocampal activity and DNRAb titers were independently predictive of memory performance. Together, or with both orbitofrontal hypermetabolism and high DNRAb titer, the accuracy of the prediction were stronger. - by Shirley Pulawski
Disclosure: The researchers report no relevant financial disclosures.