Contributions
Abstract: P530
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum Neurofilament light chain (NfL) is a promising marker of neuronal injury and is associated with disease activity in multiple sclerosis (MS) patients. However, its predictive value for development of cognitive decline in early stages of MS has not been investigated.
Aims: To investigate relationship between serum NfL levels in the early MS and evolution of cognitive decline over 9-years.
Methods: 57 patients after a first demyelinating event suggestive of MS from the study of early interferon treatment (SET) were included. Serum NfL levels were measured at screening, at baseline (intramuscular interferon beta1a initiation) and at 1 year. Age-related pathological NfL levels were defined using 90th percentile cut-off (Disanto et al.; 2017). Cognitive performance was assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test Revised (BVMTR), California Verbal Learning Test Second Edition (CVLT2) and Paced Auditory Serial Addition Test-3 seconds (PASAT-3) at baseline, at 1, 2 and 8.9 (95% confidence interval 8.8-9.0) years. NfL levels were measured using a Single Molecule Array (Simoa) assay. We applied Spearman´s correlation, Odds ratio, Chi-square test, linear and logistic regression adjusted for age, sex, treatment and cognitive performance at baseline.
Results: Higher NfL levels at screening were associated with lower CVLT2 scores at baseline (rho=-0.28; p=0.032). We did not find other correlations between early NfL levels and cross-sectional or longitudinal cognitive measures. Age-related pathological NfL levels at 1 year were observed in 9 (15.8%) patients and were associated with 4.7-fold (p=0.037) greater risk of CVLT2 decrease between 1 and 9 years compared with patients with normal NfL levels. This relationship was confirmed in adjusted logistic regression (p=0.028). There was also a trend for an association between pathological NfL level at 1 year and PASAT-3 decline over 9 years (Odds ratio 4.7; p=0.053). BVMTR and SDMT scores decline were not associated with early NfL levels.
Conclusions: Pathological serum NfL levels at disease onset were associated with verbal memory decline over long-term follow-up. Similarly as in imaging studies, the association between para-clinical markers of disease activity and cognitive measures may be substantially stronger in more advanced disease stages. In this respect, future studies on larger cohorts and with higher disease burden are warranted.
Disclosure: T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme and Merck Serono, as well as support for research activities from Biogen Idec.
B. Benova received compensation for traveling and conference fees from Novartis, Sanofi Genzyme and Biogen.
L. Kadrnozkova received compensation for travelling and conference fees from Novartis and Merck.
Z. Michalak reports no disclosures.
J. Motyl received compensation for travelling and conference fees from Novartis and Merck.
K. Kucerova received compensation for travelling and conference fees from Biogen, Novartis and Merck.
M. Andelova received compensation for travelling and conference fees from Biogen, Novartis and Merck.
C. Barro received conference travel grant from Teva and Novartis.
E. Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, Teva, Actelion and Receptos, as well as support for research activities from Biogen Idec and Merck Serono.
J. Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
D. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
This project was funded through a Biogen Sponsored Research Agreement.
Abstract: P530
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Introduction: Serum Neurofilament light chain (NfL) is a promising marker of neuronal injury and is associated with disease activity in multiple sclerosis (MS) patients. However, its predictive value for development of cognitive decline in early stages of MS has not been investigated.
Aims: To investigate relationship between serum NfL levels in the early MS and evolution of cognitive decline over 9-years.
Methods: 57 patients after a first demyelinating event suggestive of MS from the study of early interferon treatment (SET) were included. Serum NfL levels were measured at screening, at baseline (intramuscular interferon beta1a initiation) and at 1 year. Age-related pathological NfL levels were defined using 90th percentile cut-off (Disanto et al.; 2017). Cognitive performance was assessed by Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test Revised (BVMTR), California Verbal Learning Test Second Edition (CVLT2) and Paced Auditory Serial Addition Test-3 seconds (PASAT-3) at baseline, at 1, 2 and 8.9 (95% confidence interval 8.8-9.0) years. NfL levels were measured using a Single Molecule Array (Simoa) assay. We applied Spearman´s correlation, Odds ratio, Chi-square test, linear and logistic regression adjusted for age, sex, treatment and cognitive performance at baseline.
Results: Higher NfL levels at screening were associated with lower CVLT2 scores at baseline (rho=-0.28; p=0.032). We did not find other correlations between early NfL levels and cross-sectional or longitudinal cognitive measures. Age-related pathological NfL levels at 1 year were observed in 9 (15.8%) patients and were associated with 4.7-fold (p=0.037) greater risk of CVLT2 decrease between 1 and 9 years compared with patients with normal NfL levels. This relationship was confirmed in adjusted logistic regression (p=0.028). There was also a trend for an association between pathological NfL level at 1 year and PASAT-3 decline over 9 years (Odds ratio 4.7; p=0.053). BVMTR and SDMT scores decline were not associated with early NfL levels.
Conclusions: Pathological serum NfL levels at disease onset were associated with verbal memory decline over long-term follow-up. Similarly as in imaging studies, the association between para-clinical markers of disease activity and cognitive measures may be substantially stronger in more advanced disease stages. In this respect, future studies on larger cohorts and with higher disease burden are warranted.
Disclosure: T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme and Merck Serono, as well as support for research activities from Biogen Idec.
B. Benova received compensation for traveling and conference fees from Novartis, Sanofi Genzyme and Biogen.
L. Kadrnozkova received compensation for travelling and conference fees from Novartis and Merck.
Z. Michalak reports no disclosures.
J. Motyl received compensation for travelling and conference fees from Novartis and Merck.
K. Kucerova received compensation for travelling and conference fees from Biogen, Novartis and Merck.
M. Andelova received compensation for travelling and conference fees from Biogen, Novartis and Merck.
C. Barro received conference travel grant from Teva and Novartis.
E. Kubala Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme, Teva, Actelion and Receptos, as well as support for research activities from Biogen Idec and Merck Serono.
J. Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.
D. Horakova received compensation for travel, speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck Serono, Bayer Shering, and Teva, as well as support for research activities from Biogen Idec.
This project was funded through a Biogen Sponsored Research Agreement.