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.
- systemic lupus erythematosus (sle)
- spatial navigation task (snt)
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EP, CT and MM are joint first authors.
Contributors Study concept and design: EP, CT, MM, JS, BB, PW, BV, BD and DE; acquisition of data: EP, CT, EA, BB, SK, CA and CS; analysis and interpretation of data: EP, CT, MM, MS, CA, BV, BD and DE; main manuscript text: EP, CT, MM and MS. All authors contributed to manuscript drafting and revisions, with final approval prior to submission.
Funding This work was supported by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (research grant 1P01AI073693).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The research was in compliance with the Helsinki Declaration and approved by the Institutional Review Board and the Institutional Radioactive Dose Research Committee of the Northwell Health System.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available on reasonable request.
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