TY - JOUR
T1 - Brain-derived neurotrophic factor, neurofilament light and glial fibrillary acidic protein do not change in response to aerobic training in people with MS-related fatigue – a secondary analysis of a randomized controlled trial
AU - Gravesteijn, Arianne S.
AU - Beckerman, Heleen
AU - Willemse, Eline A. J.
AU - Hulst, Hanneke E.
AU - de Jong, Brigit A.
AU - Teunissen, Charlotte E.
AU - de Groot, Vincent
N1 - Funding Information: This study has been performed on behalf of the Treating Fatigue in Multiple Sclerosis: Aerobic Training, Cognitive Behavioural Therapy, Energy Conservation management (TREFAMS-ACE) Study Group: V de Groot and H Beckerman (programme coordination), A Malekzadeh, LE van den Akker, M Looijmans (until September 2013), SA Sanches (until February 2012), J Dekker, EH Collette, BW van Oosten, CE Teunissen, MA Blankenstein, ICJM Eijssen, M Rietberg (VU University Medical Center, Amsterdam); M Heine, O Verschuren, G Kwakkel, JMA Visser-Meily, IGL van de Port (until February 2012), E Lindeman (until September 2012) (Center of Excellence for Rehabilitation Medicine, University Medical Centre Utrecht and Rehabilitation Centre, De Hoogstraat, Utrecht); LJM Blikman, J van Meeteren, JBJ Bussmann, HJ Stam, RQ Hintzen (Erasmus MC, University Medical Center, Rotterdam); HGA Hacking, EL Hoogervorst, STFM Frequin (St Antonius Hospital, Nieuwegein); H Knoop, BA de Jong (until January 2014), G Bleijenberg (until April 2012) (University Medical Center St Radboud, Nijmegen); FAJ de Laat (Libra Rehabilitation Medicine & Audiology – location Leijpark, Tilburg); MC Verhulsdonck (Rehabilitation Center, Sint Maartenskliniek, Nijmegen); EThL van Munster (Jeroen Bosch Hospital, Den Bosch); CJ Oosterwijk, GJ Aarts (until March 2013) (Dutch patient organization, Multiple Sclerosis Vereniging Nederland (MSVN), The Hague). Funding Information: This work was supported by the Fonds NutsOhra (ZonMw 89000005). The funding organization had no role in the study design, data collection, data analysis, interpretation of data, writing of the report and in the decision to submit the article for publication. Publisher Copyright: © 2022
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Background: Neuroinflammation and neurodegeneration are pathological hallmarks of multiple sclerosis (MS). Brain-derived neurotrophic factor (BDNF), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are blood-based biomarkers for neurogenesis, axonal damage and astrocyte reactivity, respectively. We hypothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels. Objectives: To investigate the neuroprotective effect of aerobic training (AT) compared to a control intervention on blood-based biomarkers (i.e. BDNF, NfL, GFAP) in people with MS (pwMS). Methods: In the TREFAMS-AT (Treating Fatigue in Multiple Sclerosis - Aerobic Training) study, 89 pwMS were randomly allocated to either a 16-week AT intervention or a control intervention (3 visits to a MS nurse). In this secondary analysis, blood-based biomarker concentrations were measured in 55 patients using Simoa technology. Changes in pre- and post-intervention concentrations were compared and between-group differences were assessed using analysis of covariance (ANCOVA). Confounding effects of age, sex, MS-related disability assessed using the Expanded Disability Status Scale (EDSS), MS duration, use of disease-modifying medication, and Body Mass Index were considered. Results: Blood samples were available for 30 AT and 25 control group participants (mean age 45.6 years, 71% female, median disease duration 8 years, median EDSS score 2.5). Within-group changes in both study groups were small and non-significant, with the exception of BDNF in the control group (median (interquartile range) -2.1 (-4.7; 0)). No between-group differences were found for any biomarker: BDNF (β = 0.11, 95%CI (-3.78 to 4.00)), NfL (β = -0.04, 95%CI (-0.26 to 0.18)), and GFAP (β = -0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders. Conclusion: Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS. Trial registration: this study is registered under number ISRCTN69520623 (https://www.isrctn.com/ISRCTN695206).
AB - Background: Neuroinflammation and neurodegeneration are pathological hallmarks of multiple sclerosis (MS). Brain-derived neurotrophic factor (BDNF), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are blood-based biomarkers for neurogenesis, axonal damage and astrocyte reactivity, respectively. We hypothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels. Objectives: To investigate the neuroprotective effect of aerobic training (AT) compared to a control intervention on blood-based biomarkers (i.e. BDNF, NfL, GFAP) in people with MS (pwMS). Methods: In the TREFAMS-AT (Treating Fatigue in Multiple Sclerosis - Aerobic Training) study, 89 pwMS were randomly allocated to either a 16-week AT intervention or a control intervention (3 visits to a MS nurse). In this secondary analysis, blood-based biomarker concentrations were measured in 55 patients using Simoa technology. Changes in pre- and post-intervention concentrations were compared and between-group differences were assessed using analysis of covariance (ANCOVA). Confounding effects of age, sex, MS-related disability assessed using the Expanded Disability Status Scale (EDSS), MS duration, use of disease-modifying medication, and Body Mass Index were considered. Results: Blood samples were available for 30 AT and 25 control group participants (mean age 45.6 years, 71% female, median disease duration 8 years, median EDSS score 2.5). Within-group changes in both study groups were small and non-significant, with the exception of BDNF in the control group (median (interquartile range) -2.1 (-4.7; 0)). No between-group differences were found for any biomarker: BDNF (β = 0.11, 95%CI (-3.78 to 4.00)), NfL (β = -0.04, 95%CI (-0.26 to 0.18)), and GFAP (β = -0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders. Conclusion: Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS. Trial registration: this study is registered under number ISRCTN69520623 (https://www.isrctn.com/ISRCTN695206).
KW - Brain-derived neurotrophic factor
KW - Exercise
KW - Glial fibrillary acidic protein
KW - Multiple sclerosis
KW - Neurofilament proteins
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=85146012238&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.msard.2022.104489
DO - https://doi.org/10.1016/j.msard.2022.104489
M3 - Article
C2 - 36621163
SN - 2211-0348
VL - 70
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
M1 - 104489
ER -