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Original research
Assessing cognitive impairment in SLE: examining relationships between resting glucose metabolism and anti-NMDAR antibodies with navigational performance
  1. Elisabeth Ploran1,
  2. Chris Tang2,
  3. Meggan Mackay3,
  4. Michael Small2,
  5. Erik Anderson3,
  6. Justin Storbeck4,
  7. Brittany Bascetta4,
  8. Simran Kang4,
  9. Cynthia Aranow3,
  10. Carl Sartori3,
  11. Philip Watson5,
  12. Bruce Volpe6,
  13. Betty Diamond3 and
  14. David Eidelberg2
  1. 1Department of Psychology, Hofstra University, Hempstead, New York, USA
  2. 2Center for Neurosciences, Feinstein Institute for Medical Research, Manhasset, New York, USA
  3. 3The Center for Autoimmune, Musculoskeletal, and Hematopoietic Diseases, Feinstein Institute for Medical Research, Manhasset, New York, USA
  4. 4Department of Psychology, Queens College, Flushing, New York, USA
  5. 5Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York, USA
  6. 6Center for Biomedical Science, Feinstein Institute for Medical Research, Manhasset, New York, USA
  1. Correspondence to Dr Elisabeth Ploran; elisabeth.j.ploran{at}hofstra.edu

Abstract

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.

  • FDG-PET
  • DNRAb
  • systemic lupus erythematosus (sle)
  • spatial navigation task (snt)

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • 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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