Cerebral Lesions Considered Important Predictor of Cognitive Deficits in MOGAD

Martin W. Hummert, MD

Findings from a large, multicenter study of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) showed that near 1 in every 10 patients had neuropsychological deficits, particularly in visuomotor processing speed and semantic fluency. Notably, cerebral lesions appeared to be an important predictor of these cognitive deficits, which may be important for helping identify neuropsychological end points for future treatment trials.¹

Published in Neurology, Neurosurgery, & Psychiatry, the study aimed to determine the extent and characteristics of possible cognitive deficits in a sample of 122 patients with MOGAD. Otherwise known as the CogniMOG-Study, the longitudinal trial assessed individual cognitive performance of patients through the Paced Auditory Serial Addition Task (PASAT), the Symbol Digit Modalities Test (SDMT), and the Multiple Sclerosis Inventory Cognition (MuSIC). Patients’ performance on these assessments were standardized against normative data from health controls.

Senior author Martin W. Hummert, MD, a doctorate in the department of neurology at Hannover Medical School, in Germany, and colleagues, assessed cognitive performance at baseline and at 1-year and 2-year follow-up assessments. When exclusively including patients below the age of 60 (n = 113), results showed that at baseline, this group performed statistically discernible worse than the normative population in both MuSIC semantic fluency (mean, –0.29; 95% CI, –0.47 to –0.12) and MuSIC congruent speed (mean, –0.73; 95% CI, –1.23 to –0.23). The study sample's standardized test performance exceeded the normative population in MuSIC immediate recall list B (mean, 0.39, 95% CI (0.16-0.61), while scores on other neuropsychological tests for patients with MOGAD showed no significant deviation from the normative population.

Among participants completing at least two neuropsychological tests, 11 out of 99 (11%) showed cognitive deficits in two or more dimensions at baseline, with 36 out of 113 (32%) showing deficits in at least one test. MuSIC congruent speed had the highest proportion of patients with deficits (13 out of 77, or 17%).

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When understanding the association of demographic and clinical variables on cognitive performance, results revealed that higher age (B = –0.35; 95% CI, –0.50 to –0.20) and disease manifestation with cerebral lesions (B = –8.85; 95% CI, –13.57 to –4.14) remained negative predictors for SDMT test performance after Bonferroni correction. In contrast, higher educational level (B = 7.84; 95% CI, 3.57-12.11) was a positive predictor for SDMT test scores. Furthermore, a cerebral disease manifestation was predictive for decreased MuSIC semantic fluency test performance (B = –4.17; 95% CI, –6.10 to –2.25).

Hummert et al noted that the association between cerebral lesions and reduced SDMT and MuSIC semantic performance should be “further addressed in specific fMRI studies to address the target brain regions." They added that the study’s findings "may help to better understand the disease burden in MOGAD, better address rehabilitative needs, and identify potential neuropsychological end points for future treatment trials."

At the 2-year follow-up, patients with MOGAD showed better scores relative to baseline in SDMT ((baseline median: 59.00 vs follow-up 2 median: 60.00, P = 0.007), MuSIC immediate recall (list A)(baseline median: 14.00 vs follow-up 2 median: 17.00, P = 0.001), MuSIC delayed recall (list A)(baseline median: 6.00 vs follow-up 2 median: 7.00, P =0.01) and MuSIC congruent speed (baseline median: 24.50 vs follow-up 2 median: 22.00, P = 0.04). The proportion of patients with deficits in at least two neuropsychological tests decreased from baseline (11 out of 99, 11%) to 1-year follow-up (4 out of 49, 8%) and 2-year follow-up (0 out of 27, 0%). Similarly, overall deficits in at least one test declined from baseline (36 out of 113, 32%) to 1-year follow-up (16 out of 55, 29%) and 2-year follow-up (5 out of 34, 15%).

"Accordingly, it can be assumed that cognitive deficits in MOGAD are still rare but may mainly affect the speed of information processing, with an emphasis on the verbal dimension," the study authors wrote. "These deficits are consistent with a previous observational study reporting impaired verbal reasoning in pediatric MOGAD, as semantic fluency and congruency speed cover similar cognitive dimensions. Another study reported impaired verbal learning ability in adult MOGAD patients, which contrasts with the findings of the present CogniMOG study, as we did not find deficits in either immediate or delayed recall."

REFERENCE
1. Passoke S, Stern C, Häußler V, et al. Cognition in patients with myelin oligodendrocyte glycoprotein antibody-associated disease: a prospective, longitudinal, multicenter study of 113 patients (CogniMOG-Study). Neurol, Neurosurg, & Psych. Published online July 30, 2024. doi:10.1136/jnnp-2024-333994