No Relation Between Cognitive Impairment, Physical Disability and Serum Biomarkers in a Cohort of Progressive Multiple Sclerosis Patients

Abstract

Despite significant efforts, there is still an existing need to identify diagnostic tools that would enable fast and reliable detection of the progressive stage of multiple sclerosis (MS) and help in monitoring the disease course and/or treatment effects. The aim of this prospective study in a group of people with progressive MS was to determine whether changes in the levels of selected serum biomarkers and in cognitive function may predict disease progression, and therefore refine the decision-making process in the evaluation of MS patients. Forty two (42) patients with progressive MS completed all the study procedures; the mean duration of follow-up was 12.97 months. During the observation period, serum concentration of chitinase-3 like-protein-1 (CHI3L1/YKL-40) decreased significantly in the whole study group (from 4034.95 ± 262.62 to 2866.43 ± 173.37; p = 0.0005), as well as in subgroups of people with secondary progressive and primary progressive MS (SPMS: from 3693.81 ± 388.68 to 2542.76 ± 256.59; p = 0.0207; and PPMS: from 4376.09 ± 353.27 to 3190.09 ± 233.22; p = 0.0089, respectively). A significant worsening of Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) scores was detected in the whole study group (from 1.18 ± 0.14 to 1.34 ± 0.15; p = 0.0331) as well as in the PPMS subgroup (from 1.04 ± 0.18 to 1.26 ± 0.20; p = 0.0216). No correlations between the analyzed molecular parameters or the results of neuropsychological tests and physical disability were observed. In conclusion, an emphasis should be placed on furthering the search for multimodal biomarkers of disease progression, especially in the PMS population, based on simultaneous analysis of several factors, such as blood biomarkers and cognitive profiles.

Keywords: Brief International Cognitive Assessment for Multiple Sclerosis; biomarkers; chitanse-3 like-protein-1; cognitive impairment; neurofilament light chain; progression; progressive multiple sclerosis.

Figure 1

Flowchart of enrollment and follow-up of participants.

Figure 2

Changes in mean EDSS during study period. Data presented as means (points) with SE (whiskers). Values did not reach statistical significance. EDSS—Expanded Disability Status Scale, PPMS—primary progressive multiple sclerosis, SPMS—secondary progressive multiple sclerosis.

Figure 3

Changes in serum YKL-40 levels. Data presented as means with standard error (SE). “*” statistical significance p < 0.05. Figure S1A,B regarding changes in serum levels of NfL and CXCL-13, respectively, are included in Supplementary Materials. PPMS—primary progressive multiple sclerosis, SPMS—secondary progressive multiple sclerosis, NfL—neurofilament light chain, CXCL-13—C-X-C Motif Chemokine Ligand 13, YKL-40—chitanse-3 like-protein-1.

Figure 4

(A–C): Correlations between EDSS and serum biomarkers change. Values did not reach statistical significance. (A) PMS; (B) PPMS and (C) SPMS. EDSS—Expanded Disability Status Scale, PMS—progressive multiple sclerosis, PPMS—primary progressive multiple sclerosis, SPMS—secondary progressive multiple sclerosis, NfL—neurofilament light chain, CXCL-13—C-X-C Motif Chemokine Ligand 13, YKL-40—chitanse-3 like-protein-1.

Figure 5

Generalized linear model with repeated measures for BICAMS (A), BVMT-R (B), CVLT (C), SDMT (D), VFT (E,F), and SCWT (G,H). Data presented as means with standard error (SE). Values did not reach statistical significance. As previously, blue indicates PPMS group and red indicates SPMS group. PPMS—primary progressive multiple sclerosis, SPMS—secondary progressive multiple sclerosis.

Figure 5

Generalized linear model with repeated measures for BICAMS (A), BVMT-R (B), CVLT (C), SDMT (D), VFT (E,F), and SCWT (G,H). Data presented as means with standard error (SE). Values did not reach statistical significance. As previously, blue indicates PPMS group and red indicates SPMS group. PPMS—primary progressive multiple sclerosis, SPMS—secondary progressive multiple sclerosis.