Assessing cognitive impairment in SLE: examining relationships between resting glucose metabolism and anti-NMDAR antibodies with navigational performance

OBJECTIVE: Resting Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) brain imaging and neuropsychological testing were used to investigate the usefulness of a spatial navigation task (SNT) as a performance benchmark for cognitive impairment related to anti-N-methyl D-aspartate (anti-NMDA) receptor antibodies (DNRAb) in SLE. METHODS: Neuropsychological assessments, including a desktop 3-D virtual SNT, were performed on 19 SLE participants and 9 healthy control (HC) subjects. SLE participants had stable disease activity and medication doses and no history of neuropsychiatric illness or current use of mind-altering medications. Resting FDG-PET scans were obtained on all SLE participants and compared with a historical set from 25 age-matched and sex-matched HCs. Serum DNRAb titres were measured by ELISA. RESULTS: 11/19 (58%) of SLE participants failed to complete the SNT (SNT−) compared with 2/9 (22%) of HCs. Compared with 7/9 (78%) in HCs, only 2/9 (22%; p=0.037) of SLE participants with high serum DNRAb titres completed the SNT, in contrast to 6/10 (60%; p=0.810) in SLE participants with low DNRAb titres. Voxel-wise comparison of FDG-PET scans between the 8 SLE participants successfully completing the SNT task (SNT+) and the 11 SNT− SLE participants revealed increased metabolism in the SNT+ participants (p<0.001) in the left anterior putamen/caudate, right anterior putamen, left prefrontal cortex (BA 9), right prefrontal cortex (BA 9/10) and left lateral and medial frontal cortex (BA 8). Compared with HCs, the SNT+ group demonstrated increased metabolism in all regions (p<0.02) except for the right prefrontal cortex (BA 9), whereas the SNT− group demonstrated either significantly decreased or similar metabolism in these seven regions. CONCLUSIONS: SNT performance is associated with serum DNRAb titres and resting glucose metabolism in the anterior putamen/caudate and frontal cortex, suggesting compensatory neural recruitment in SNT-associated regions is necessary for successful completion of the task. The SNT therefore has potential for use as a marker for SLE-mediated cognitive impairment.