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.
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.
ABSTRACT
While the Validity Indicator Profile (VIP) and the Test of Memory Malingering (TOMM) are designed to limit the influence of actual cognitive impairment on successful performance, the extent to which cognitive dysfunction does play a role in the assessment of effort should be verified in distinct clinical groups. To date, little research has been conducted on VIP performance in individuals diagnosed with a psychotic disorder. Fifty-four patients with either schizophrenia or schizoaffective disorder were administered the VIP, TOMM, Short Test of Mental Status, and the Wide Range Achievement Test-4 Reading subtest. Specificity rates were compared between tests, with normative data, and with published specificity rates in psychiatric samples. Results indicate that the use of the VIP with psychotic-disordered individuals will generate increased invalid performance profiles, whereas the TOMM is more resilient in this population. Significantly, mental status and estimated intellectual ability were predictive of classifications on the VIP Verbal subtest and the TOMM.
