Brain MRI disease burden and sex differences in cognitive performance of patients with multiple sclerosis.

BACKGROUND: Although there is evidence that shows worse cognitive functioning in male patients with multiple sclerosis (MS), the role of brain pathology in this context is under-investigated. OBJECTIVE: To investigate sex differences in cognitive performance of MS patients, in the context of brain pathology and disease burden. METHODS: Brain MRI, neurological examination, neuropsychological assessment (Brief International Cognitive Assessment in MS-BICAMS, and Paced Auditory Verbal Learning Test-PASAT), and patient-reported outcome questionnaires were performed/administered in 1052 MS patients. RESULTS: Females had higher raw scores in the Symbol Digit Modalities Test (SDMT) (57.0 vs. 54.0; p < 0.001) and Categorical Verbal Learning Test (CVLT) (63.0 vs. 57.0; p < 0.001), but paradoxically, females evaluated their cognitive performance by MS Neuropsychological Questionnaire as being worse (16.6 vs 14.5, p = 0.004). Females had a trend for a weaker negative correlation between T2 lesion volume and SDMT ([Formula: see text] = - 0.37 in females vs. - 0.46 in men; interaction p = 0.038). On the other hand, women had a trend for a stronger correlation between Brain Parenchymal Fraction (BPF) and a visual memory test (Spearman's [Formula: see text] = 0.31 vs. 0.21; interaction p = 0.016). All these trends were not significant after correction for false discovery rate. CONCLUSIONS: Although, females consider their cognition as worse, males had at a group level slightly worse verbal memory and information processing speed. However, the sex differences in cognitive performance were smaller than the variability of scores within the same sex group. Brain MRI measures did not explain the sex differences in cognitive performance among MS patients.

Isolated Cognitive Decline in Neurologically Stable Patients with Multiple Sclerosis.

(1) Background: Cognitive deterioration is an important marker of disease activity in multiple sclerosis (MS). It is vital to detect cognitive decline as soon as possible. Cognitive deterioration can take the form of isolated cognitive decline (ICD) with no other clinical signs of disease progression present. (2) Methods: We investigated 1091 MS patients from the longitudinal GQ (Grant Quantitative) study, assessing their radiological, neurological, and neuropsychological data. Additionally, the confirmatory analysis was conducted. Clinical disease activity was defined as the presence of new relapse or disability worsening. MRI activity was defined as the presence of new or enlarged T2 lesions on brain MRI. (3) Results: Overall, 6.4% of patients experienced cognitive decline and 4.0% experienced ICD without corresponding clinical activity. The vast majority of cognitively worsening patients showed concomitant progression in other neurological and radiologic measures. There were no differences in disease severity between completely stable patients and cognitively worsening patients but with normal cognition at baseline. (4) Conclusions: Only a small proportion of MS patients experience ICD over short-term follow-up. Patients with severe MS are more prone to cognitive decline; however, patients with normal cognitive performance and mild MS might benefit from the early detection of cognitive decline the most.

Cognitive clinico-radiological paradox in early stages of multiple sclerosis.

Objective: To investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations. Methods: A total of 1052 patients were included in this large cross-sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed. Results: Weak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman's rho = 0.05-0.21), with short disease duration (<2 years; rho = 0.01-0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho = 0.08-0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01-0.20), and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01-0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho = 0.24-0.50), with longer disease duration (>15 years; rho = 0.26-0.53), higher EDSS (≥5.0; rho = 0.23-0.39), greater T2 lesion volume (highest quartile; >5.33 mL; rho = 0.16-0.32), and lower brain parenchymal fraction (lowest quartile; <83.71; rho = 0.13-0.46). The majority of these observed results were confirmed by significant interactions (P ≤ 0.01) using continuous variables. Interpretation: The association between structural brain damage and functional cognitive impairment is substantially weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies, and clinical practice.

Influence of nationality on the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).

OBJECTIVE: In answer to the call for improved accessibility of neuropsychological services to the international community, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS; MS) was validated in multiple, non-English-speaking countries. It was created to monitor processing speed and learning in MS patients, including abbreviated versions of the Symbol Digit Modalities Test, California Verbal Learning Test, 2nd Edition, and the Brief Visuospatial Memory Test, Revised. The objective of the present study was to examine whether participant nationality impacts performance above and beyond common demographic correlates. METHOD: We combined published data-sets from Argentina, Brazil, Czech Republic, Iran, and the U.S.A. resulting in a database of 1,097 healthy adults, before examining the data via multiple regression. RESULTS: Nationality significantly predicted performance on all three BICAMS tests after controlling for age and years of education. Interactions among the core predictor variables were non-significant. CONCLUSION: We demonstrated that nationality significantly influences BICAMS performance and established the importance of the inclusion of a nationality variable when international norms for the BICAMS are constructed.

Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome.

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.