Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis

Martin Langeskov-Christensen; Lars Grøndahl Hvid; Mikkel Karl Emil Nygaard; Steffen Ringgaard; Henrik Boye Jensen; Helle Hvilsted Nielsen; Thor Petersen; Egon Stenager; Simon Fristed Eskildsen; Ulrik Dalgas

doi:10.1212/WNL.0000000000011241

Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis

Martin Langeskov-Christensen^*, Lars Grøndahl Hvid, Mikkel Karl Emil Nygaard, Steffen Ringgaard, Henrik Boye Jensen, Helle Hvilsted Nielsen, Thor Petersen, Egon Stenager, Simon Fristed Eskildsen, Ulrik Dalgas

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS).

METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle.

RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group.

CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.

CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555.

CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.

Original language	English
Journal	Neurology
Volume	96
Issue	2
Pages (from-to)	e203-e213
Number of pages	11
ISSN	0028-3878
DOIs	https://doi.org/10.1212/WNL.0000000000011241
Publication status	Published - Jan 2021

Keywords

Adult
Brain/diagnostic imaging
Cross-Over Studies
Denmark/epidemiology
Exercise/physiology
Female
Follow-Up Studies
High-Intensity Interval Training/methods
Humans
Magnetic Resonance Imaging/methods
Male
Middle Aged
Multiple Sclerosis/diagnostic imaging
Treatment Outcome

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10.1212/WNL.0000000000011241

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@article{7990239ef14b43f78c54d7d10ed662cf,

title = "Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis",

abstract = "OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS).METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle.RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group.CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555.CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.",

keywords = "Adult, Brain/diagnostic imaging, Cross-Over Studies, Denmark/epidemiology, Exercise/physiology, Female, Follow-Up Studies, High-Intensity Interval Training/methods, Humans, Magnetic Resonance Imaging/methods, Male, Middle Aged, Multiple Sclerosis/diagnostic imaging, Treatment Outcome",

author = "Martin Langeskov-Christensen and {Gr{\o}ndahl Hvid}, Lars and Nygaard, {Mikkel Karl Emil} and Steffen Ringgaard and Jensen, {Henrik Boye} and Nielsen, {Helle Hvilsted} and Thor Petersen and Egon Stenager and Eskildsen, {Simon Fristed} and Ulrik Dalgas",

note = "{\textcopyright} 2020 American Academy of Neurology.",

year = "2021",

month = jan,

doi = "10.1212/WNL.0000000000011241",

language = "English",

volume = "96",

pages = "e203--e213",

journal = "Neurology",

issn = "0028-3878",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "2",

}

Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis. / Langeskov-Christensen, Martin ; Grøndahl Hvid, Lars ; Nygaard, Mikkel Karl Emil et al.
In: Neurology, Vol. 96, No. 2, 01.2021, p. e203-e213.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis

AU - Langeskov-Christensen, Martin

AU - Grøndahl Hvid, Lars

AU - Nygaard, Mikkel Karl Emil

AU - Ringgaard, Steffen

AU - Jensen, Henrik Boye

AU - Nielsen, Helle Hvilsted

AU - Petersen, Thor

AU - Stenager, Egon

AU - Eskildsen, Simon Fristed

AU - Dalgas, Ulrik

PY - 2021/1

Y1 - 2021/1

N2 - OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS).METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle.RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group.CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555.CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.

AB - OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS).METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle.RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group.CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555.CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.

KW - Adult

KW - Brain/diagnostic imaging

KW - Cross-Over Studies

KW - Denmark/epidemiology

KW - Exercise/physiology

KW - Female

KW - Follow-Up Studies

KW - High-Intensity Interval Training/methods

KW - Humans

KW - Magnetic Resonance Imaging/methods

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/diagnostic imaging

KW - Treatment Outcome

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U2 - 10.1212/WNL.0000000000011241

DO - 10.1212/WNL.0000000000011241

M3 - Journal article

C2 - 33262230

SN - 0028-3878

VL - 96

SP - e203-e213

JO - Neurology

JF - Neurology

IS - 2

ER -

Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis

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Keywords

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