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

Abstract

ObjectiveResting 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.MethodsNeuropsychological 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.Results11/19 (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.ConclusionsSNT 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.

Cognitive dysfunction in autoimmune rheumatic diseases

“…Functional MRI studies have shown increased functional connectivity in core resting-state networks in SLE patients that correlate with reduced cognitive performance compared with healthy controls [37]. FDG-PET imaging highlighted hypermetabolic regions that corresponded with increased serum anti-NMDAR antibodies in SLE patients with CD and did not correlate with disease duration, activity, medications or comorbidities [26,27]. These studies highlight a potential role for these imaging techniques in objectively diagnosing and monitoring CD in SLE patients.…”

“…In fact, there is evidence for the involvement of multiple aspects of the immune system in NPSLE, including neurotoxic autoantibodies, pro-inflammatory cytokines and cell-mediated effects, in conjunction with abnormalities in neuroimmune interfaces including the choroid plexus and blood-brain barrier which allow systemic autoimmune drivers into the central nervous system [21,24]. Specifically, several studies have pointed to increased systemic levels of cytokines such as interleukin 6 (IL-6) and neurotoxic anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in SLE patients with CD [25][26][27]. In addition, type I interferon (IFN-I) and anti-NMDAR antibodies were shown to enhance microglia activation, leading to aberrant synaptic pruning with subsequent CD [28,29].…”

Using the Mouse to Model Human Diseases: Cognitive Impairment in Systemic Lupus Erythematosus

“…Hypermetabolism in 5 of these regions correlated with poor performance on a memory test. Further, we showed a significant correlation between serum DNRAb, the performance on a spatial navigation task, and resting glucose metabolism in the anterior putamen and frontal cortex 41 . DTI images revealed the presence of regions of decreased microstructural integrity (measured by FA) structurally linked to the hypermetabolic regions.…”

Relationship between Glucose Metabolism Abnormalities and Neuronal Autophagy and Apoptosis in Patients with Ischemic Stroke and Cognitive Impairment

“…Glucose metabolism abnormalities will increase the risk of cognitive impairment of patients (Ploran et al, 2019). Viswanathan et al (2019) found that the incidence of Alzheimer's disease in patients with type 2 diabetes is significantly higher than that in patients with normal glucose metabolism abnormalities, and the risk ratio is as high as 25%.…”