Accepted Manuscript The effect of exercise training on fitness in multiple sclerosis: A meta-analysis M.E. Platta, I. Ensari, R.W. Motl, L.A. Pilutti PII:

S0003-9993(16)00091-5

DOI:

10.1016/j.apmr.2016.01.023

Reference:

YAPMR 56446

To appear in:

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION

Received Date: 26 October 2015 Revised Date:

6 January 2016

Accepted Date: 28 January 2016

Please cite this article as: Platta ME, Ensari I, Motl RW, Pilutti LA, The effect of exercise training on fitness in multiple sclerosis: A meta-analysis, ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2016), doi: 10.1016/j.apmr.2016.01.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

RUNNING HEAD: Fitness in multiple sclerosis

RI PT

Title: The effect of exercise training on fitness in multiple sclerosis: A meta-analysis Authors: M.E. Platta, I. Ensari, R.W. Motl, L.A. Pilutti

SC

From the Department of Kinesiology and Community Health, University of Illinois Urbana-

M AN U

Champaign, Urbana, IL, USA

Acknowledgements:

This research received no specific funding from any agency.

TE D

Disclosure Statement:

Dr. Motl reports a financial relationship with EMD Serono, Acorda Therapeutics, and Biogen

EP

Idec, outside the submitted work. The other authors have no disclosures.

Corresponding author: Lara A Pilutti, PhD, Department of Kinesiology and Community

AC C

Health, University of Illinois Urbana-Champaign, 213 Freer Hall, Urbana, IL 61801, USA. Phone: 217-333-6126. Fax: 217-244-7322. Email: [email protected]

For correspondence and reprints, contact Lara A. Pilutti, Ph.D., Department of Kinesiology and Community Health, University of Illinois, 213 Freer Hall, Urbana, IL 61801, email: [email protected].

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 1 The effect of exercise training on fitness in multiple sclerosis: A meta-analysis

1

Objectives: To provide a quantitative synthesis of randomized controlled trials (RCT) examining

3

the effect of exercise training on muscular and cardiorespiratory fitness in persons with MS.

4

Data Sources: Three electronic databases, Pubmed, Google Scholar and Web of Science were

5

searched for all relevant articles published up until October 2014.

6

Study Selection: Keywords included “exercise” OR “aerobic” OR “strength” OR “resistance

7

training” OR “cardiorespiratory” AND “multiple sclerosis”. Trials examining the effect of

8

exercise training on muscular and/or cardiorespiratory fitness parameters were included.

9

Data Extraction: The initial search yielded 1501 articles of which 62 were reviewed in detail

10

and 20 RCTs met the inclusion criteria and provided enough data to compute effect sizes (ESs;

11

Cohen d). The meta-analyses was conducted using Comprehensive Meta-Analysis software and a

12

random-effects model was used to compute the overall or mean ES per fitness parameter.

13

Data synthesis: The mean ES was 0.27 (SE=0.05, 95% CI=0.17-0.38, z=5.05, p< .001) for

14

muscular fitness outcomes and 0.47 (SE=0.09, 95% CI=0.30-0.65, z=5.40, p< .001) for

15

cardiorespiratory fitness outcomes. The weighted mean ES was not heterogeneous for muscular

16

(Q=11.09, df=13, p=.60, I²=0.00) or cardiorespiratory (Q=7.83, df=9, p=0.55, I²=0.00) fitness

17

outcomes.

18

Conclusions: The cumulative evidence supports that exercise training is associated with

19

changes in muscular (small in magnitude) and cardiorespiratory (moderate in magnitude) fitness

20

outcomes in persons with MS. Such an indication of magnitude is important for clinical research

21

and practice by providing an evidence-based estimate of the actual benefit that exercise training

22

confers on physiological fitness.

23

Keywords: exercise; fitness; muscular; cardiorespiratory; multiple sclerosis

AC C

EP

TE D

M AN U

SC

RI PT

2

ACCEPTED MANUSCRIPT

Abbreviations

25

1-RM = 1-repetition maximum

26

ES = effect size

27

MS = multiple sclerosis

28

Nm = Newton meters

29

RCT = randomized controlled trial

30

VO2peak = peak aerobic capacity

31

Wp = peak power output

M AN U

32 33 34 35

40 41 42 43 44 45 46

EP

39

AC C

38

TE D

36 37

SC

24

RI PT

Fitness in multiple sclerosis 2

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 3 47

Introduction Multiple sclerosis (MS) is a neurological disease characterized by inflammatory attacks

49

within the central nervous system that result in axonal demyelination and transection as well as

50

neurodegeneration.1 The pathophysiological processes associated with the disease result in

51

impairments in various domains including walking, cognition, and symptomatic changes such as

52

depression and fatigue. The consequences of MS further compromise participation in physical

53

activity and this results in significant detraining (i.e., physiological deconditioning), particularly

54

in the domains of muscular and cardiorespiratory fitness.2 Muscular fitness reflects the body’s

55

ability for generating and maintaining muscular force via skeletal muscle contraction and is

56

commonly measured as muscular strength (e.g., peak force) and endurance (e.g., maximum

57

repetitions). Cardiorespiratory fitness reflects the body’s ability for delivering, extracting, and

58

using oxygen for prolonged endurance exercise and is typically measured as peak aerobic

59

capacity (VO2peak), peak power output (Wp), and anaerobic or lactate threshold (l/mmol). The

60

maintenance of muscular and cardiorespiratory fitness is critical for preserving and restoring

61

physical functioning and participation among persons with MS.3

SC

M AN U

TE D

There is evidence that both muscular and cardiorespiratory fitness are impaired in persons

EP

62

RI PT

48

with MS. For example, one study of 15 participants with MS and 15 healthy controls

64

demonstrated that persons with MS had significantly lower peak torque production in the

65

nondominant knee extensors, dominant knee flexors, and nondominant knee flexors compared to

66

healthy controls.4 This has been replicated in other studies.5,6 Similarly, cardiorespiratory fitness,

67

based on VO2peak, was 28% higher in a sample of 25 healthy controls compared to 25 participants

68

with MS,7 and such deficits have been replicated in other studies.6,8,9 The detraining and loss of

69

fitness in persons with MS combined with the importance of physiological fitness for functional

AC C

63

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 4 70

and symptomatic outcomes underscores the importance of developing and evaluating the

71

efficacy of interventions that target indices of muscular and cardiorespiratory fitness.

72

Exercise training probably reflects the intervention modality with the best likelihood and relevance for improving physiological fitness in persons with MS. There is evidence for the

74

benefits of resistance and aerobic training for improving physiological fitness in persons with

75

MS.10–12 For example, one systematic review reported that 8-20 weeks of moderate intensity

76

(i.e., 10-12 repetitions @ 70-80% 1-repetition maximum (1-RM)) resistance training performed

77

2 to 3 times per week increased muscular strength in persons with MS; there were insufficient

78

data for demonstrating a change in muscular endurance.13 That review further reported that

79

moderate intensity (i.e., 60-80% Wp or 60% VO2peak) aerobic exercise training, 2 to 3 times a

80

week for 30 to 60 minutes increased cardiorespiratory fitness (VO2peak) in persons with MS.13

SC

M AN U

81

RI PT

73

Those data are promising, but have important limitations that can be overcome in a metaanalysis. The studies often suffer from small sample sizes resulting in non-significant effects

83

resulting in the possible interpretation of no consistent or definitive effect of exercise training on

84

fitness. The studies and literature review do not provide an indication of the magnitude of

85

improvement in fitness outcomes following exercise training that can be provided through meta-

86

analysis. Such an indication of magnitude is important for clinical research and practice by

87

providing an evidence-based estimate of the actual benefit that exercise training may confer on

88

physiological fitness. We further note that there is likely variability in the effect of exercise

89

training on fitness adaptations, and this can be quantified using moderator analysis in meta-

90

analysis. This will be important for indicating the characteristics of exercise or the sample that

91

maximize the improvement in fitness outcomes.

AC C

EP

TE D

82

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 5 92

We undertook a meta-analysis for providing a quantitative assessment of the effect of exercise training on muscular and cardiorespiratory fitness outcomes in persons with MS. To do

94

this, we conducted a systematic and comprehensive meta-analysis of published randomized

95

controlled trials (RCTs) involving exercise training and MS that included outcomes of muscular

96

and cardiorespiratory fitness. We hypothesized that exercise training would be associated with

97

improvements in muscular and cardiorespiratory fitness outcomes and that these improvements

98

would be small to moderate in magnitude based on previous meta-analyses of exercise training

99

on other outcomes (e.g., walking, fatigue, and quality of life) in MS.14–17

SC

RI PT

93

101

M AN U

100

Methods

This meta-analysis was conducted consistent with the Meta-analysis of Observational

103

Studies in Epidemiology (MOOSE) framework,18 and a visual description of our step-by-step

104

methods is provided in Figure 1. We conducted a search PubMed and Web of Science using the

105

keywords “exercise” AND “aerobic” OR “strength” OR “resistance” OR “resistance training”

106

OR “cardiorespiratory” OR “fitness” AND “multiple sclerosis”. We included RCTs that were

107

published up to October 2014. We initially retrieved 1,501 articles of which 1,439 were excluded

108

for the following reasons: duplicates (n=880), not primary research articles (i.e., reviews, meta-

109

analyses, abstracts) (n=230), no inclusion of exercise training (n=163) or persons with MS

110

(n=104). We further excluded studies that were non-RCTs (n=44) or did not include fitness

111

measures (n=18). We further searched the bibliographies of the retrieved articles and reviewed a

112

total of 62 articles in detail. Of these articles, there were 42 without an exercise training

113

manipulation, appropriate control condition or randomization, or objective and usable fitness

114

outcome data, and these studies were excluded. If the papers did not include sufficient

AC C

EP

TE D

102

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 6 information for calculating effect sizes (ES), we contacted the authors for further information.

116

We included RCTs (i.e., studies that compared exercise training vs. no-treatment control and

117

stated assigning participants to conditions randomly) that administered measures of

118

cardiorespiratory or muscular fitness (e.g., VO2peak, isokinetic strength) pre-post intervention. We

119

excluded RCTs that did not include persons with MS, an objective fitness outcome, or an

120

appropriate exercise training intervention. Exercise was defined as a planned, structured, and

121

repetitive form of physical activity conducted over an extended period of time with the goal of

122

improving health-related fitness (i.e., cardiorespiratory, muscular, motor, metabolic, or

123

morphological components).19 This resulted in a total of 20 RCTs from 21 publications that were

124

included in the meta-analysis (Table 1).7,10,12,20–37

SC

M AN U

125

RI PT

115

We computed ESs expressed as Cohen’s d.38 To do this, we computed the mean change from before to after exercise training and subtracted the mean change of the control condition.

127

The resulting difference in mean change between the conditions was then divided by the baseline

128

standard deviation (SD) pooled between conditions. The ESs were calculated so that a positive

129

ES indicated an improvement in fitness levels after exercise training, whereas a negative ES

130

indicated a worsening of fitness levels in the exercise condition compared with control. Separate

131

ESs were calculated per dependent variable (i.e., some studies had multiple fitness outcomes) as

132

well as per type of exercise (i.e., some studies had more than one type of exercise training

133

modality or condition). The overall analysis took place using a single ES per study (i.e., an

134

average ES when there was more than one ES computed by the software). This was necessary as

135

multiple ESs from the same study are not independent.39 The lack of independence can bias the

136

standard error (SE) for judging the significance of the overall ES and multiple ESs from one

137

study bias the overall ES disproportionately compared with the studies that have a single ES.39

AC C

EP

TE D

126

ACCEPTED MANUSCRIPT Fitness in multiple sclerosis 7 138

The ESs along with the associated standard errors (SEs) were entered into the Comprehensive Meta-analysis Software,a Version 2.0. The analyses were conducted separately

140

for the muscular and cardiorespiratory fitness outcomes. We used a random-effects model for

141

computing the overall or mean ES (for each fitness outcome) as this model assumes that the

142

samples come from populations with different ESs and that the true effect differs between

143

studies.39 We further computed a 95% confidence interval (CI) around the mean ES. An overall

144

Q value and I2 value were calculated to test for homogeneity of variance among ESs. The Q

145

value is a measure of variance among the ESs and a statistically significant (p

Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis.

To provide a quantitative synthesis of randomized controlled trials (RCTs) examining the effect of exercise training on muscular and cardiorespiratory...
2MB Sizes 3 Downloads 13 Views