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Metabolic and microstructural alterations in the SLE brain correlate with cognitive impairment
Meggan Mackay, … , Betty Diamond, David Eidelberg
Meggan Mackay, … , Betty Diamond, David Eidelberg
Published January 10, 2019
Citation Information: JCI Insight. 2019;4(1):e124002. https://doi.org/10.1172/jci.insight.124002.
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Research Article Neuroscience

Metabolic and microstructural alterations in the SLE brain correlate with cognitive impairment

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Abstract

To address challenges in the diagnosis of cognitive dysfunction (CD) related to systemic lupus erythematosus–associated (SLE-associated) autoimmune mechanisms rather than confounding factors, we employed an integrated approach, using resting-state functional (FDG-PET) and structural (diffusion tensor imaging [DTI]) neuroimaging techniques and cognitive testing, in adult SLE patients with quiescent disease and no history of neuropsychiatric illness. We identified resting hypermetabolism in the sensorimotor cortex, occipital lobe, and temporal lobe of SLE subjects, in addition to validation of previously published resting hypermetabolism in the hippocampus, orbitofrontal cortex, and putamen/GP/thalamus. Regional hypermetabolism demonstrated abnormal interregional metabolic correlations, associated with impaired cognitive performance, and was stable over 15 months. DTI analyses demonstrated 4 clusters of decreased microstructural integrity in white matter tracts adjacent to hypermetabolic regions and significantly diminished connecting tracts in SLE subjects. Decreased microstructural integrity in the parahippocampal gyrus correlated with impaired spatial memory and increased serum titers of DNRAb, a neurotoxic autoantibody associated with neuropsychiatric lupus. These findings of regional hypermetabolism, associated with decreased microstructural integrity and poor cognitive performance and not associated with disease duration, disease activity, medications, or comorbid disease, suggest that this is a reproducible, stable marker for SLE-associated CD that may be may be used for early disease detection and to discriminate between groups, evaluate response to treatment strategies, or assess disease progression.

Authors

Meggan Mackay, An Vo, Chris C. Tang, Michael Small, Erik W. Anderson, Elisabeth J. Ploran, Justin Storbeck, Brittany Bascetta, Simran Kang, Cynthia Aranow, Carl Sartori, Philip Watson, Bruce T. Volpe, Betty Diamond, David Eidelberg

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Figure 1

Abnormal hypermetabolic regions in SLE.

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Abnormal hypermetabolic regions in SLE.
Top: Voxel-wise comparison of th...
Top: Voxel-wise comparison of the FDG-PET scans between the combined SLE-1/2 cohorts (n = 37) and healthy controls (HCs; n = 25) revealed significant increases in resting glucose metabolism in SLE subjects in the hippocampus (A and B), orbitofrontal cortex (BA 11) (C and D), and putamen/GP/thalamus (E), the same regions independently identified in SLE-1 (1) and SLE-2 (Supplemental Data). Three new hypermetabolic regions identified in the SLE-1/2 subjects include the SMC (F), occipital lobe (BA 19) (G), and temporal lobe (BA 37) (H). (Peak voxel of each cluster was significant at P < 0.001, uncorrected. Clusters for the hippocampus, putamen/GP/thalamus, and SMC were also significant at P < 0.05, corrected for cluster extent [Table 3]. Clusters were displayed using a red-yellow scale thresholded at P < 0.005 superimposed on a MRI template.). Bottom: Metabolism in these regions was significantly higher (P < 0.002) in the SLE-1/2 subjects (triangles) than in the healthy controls (circles) but not different between the SLE-1 (white triangles) and SLE-2 (black triangles) subjects (P > 0.41). (Error bar represents standard error of the mean. Arrow represents Student’s t test of SLE-1/2 subjects vs. HCs.)

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