Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Abstract

ObjectiveTo investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations.MethodsA 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.ResultsWeak 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.InterpretationThe 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.

Cognitive impairment in early MS: contribution of white matter lesions, deep grey matter atrophy, and cortical atrophy

“…In contrast, CI of all included patients was confirmed through detailed NPA by an experienced neuropsychologist. Although in accordance with the Germany guideline on neuropsychological evaluation [25], our criterion, again introduced in retrospect for quality assurance, of a documented performance score below − 1z in at least two domains is liberal compared to other studies [4][5][6][7][8][9]11]. However, in these studies, cohorts with higher EDSS and longer disease durations were investigated (more than 10 years [4, 6-9, 11] and more than 7 years [5], respectively).…”

“…One of the earliest magnetic resonance imaging (MRI) studies on CI in MS [2] reported a strong relationship between CI and white matter lesions (WML) compatible with the classic idea of a disconnection syndrome [3]. In later MRI studies, relations of CI to deep and cortical grey matter (GM) atrophy were reported [4][5][6][7][8][9][10][11]. When we, to the best of our knowledge, reviewed the ten structural brain MRI studies on CI in MS, with the highest numbers of CI patients included [4][5][6][7][8][9][10][11][12][13], we observed inconsistent results with regard to the contribution of WML load and GM atrophy to CI in MS.…”

Clinical trials for multiple sclerosis: Outcome measures and impact on cognitive function

“…long disease duration, old age, high physical disability, high MRI lesion load and high brain atrophy). 22 This association is also the case with brain atrophy. In contrast, a recent longitudinal study showed that T2 lesion volume and its change at earlier time points remained predictive of disability, even after 20 years, in patients with clinically isolated syndrome.…”

“…[18][19][20] In addition, the magnitude of the association was highly variable among studies. 22 This association is also the case with brain atrophy. A recent cross-sectional study of a large cohort of well-defined patients with relapsing-remitting MS (RRMS) showed that the strength of the association between brain MRI measures and CI was relatively low in patients with low disease burden (i.e.…”

Non‐motor symptoms in multiple sclerosis

“…short disease duration, young age, low physical disability, low MRI lesion load and low brain atrophy), whereas it was high in those with a high disease burden (i.e. long disease duration, old age, high physical disability, high MRI lesion load and high brain atrophy) . He also mentioned the recent reports utilizing non‐conventional brain imaging, such as magnetizing transfer imaging and diffusion tensor imaging.…”