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Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson's disease
Parkinsonism and Related Disorders 18 (2012) 974e977
Contents lists available at SciVerse ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson’s disease S.S. Paul a, C.G. Canning a, C. Sherrington b, V.S.C. Fung c, d, * a
Clinical & Rehabilitation Sciences Research Group, Faculty of Health Sciences, University of Sydney, Sydney, Australia Musculoskeletal Division, The George Institute for Global Health, University of Sydney, Sydney, Australia c Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia d Sydney Medical School, University of Sydney, Sydney, Australia b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 February 2012 Received in revised form 17 April 2012 Accepted 3 May 2012
Background: Reduced muscle power (speed strength) is associated with increased fall risk and reduced walking speed in people with Parkinson’s disease (PD) as well as in the general older population. This study aimed to determine the relative contribution of motor impairments (bradykinesia, tremor, rigidity and weakness) to reduced leg muscle power in people with PD. Methods: Eighty-two people with PD were tested while “on” medication. Leg extensor muscle strength and muscle power were measured using pneumatic variable resistance equipment. Lower limb bradykinesia, rigidity and tremor were measured using the Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale. Associations between motor impairments and leg muscle power were examined using linear regression. Results: Univariate models revealed that muscle strength (R2 ¼ 0.84), bradykinesia (R2 ¼ 0.05) and rigidity (R2 ¼ 0.05) were significantly associated with leg muscle power, while tremor was not. A multivariate model including bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg muscle power. This model revealed reduced muscle strength to be the major determinant of reduced muscle power (b ¼ 0.7), while bradykinesia was a minor contributor to reduced muscle power (b ¼ 0.1), even when accounting for age and gender. Conclusions: The findings that reduced strength and bradykinesia contribute to reduced muscle power in people with PD tested “on” medication suggest that these impairments are potential targets for physical interventions. Ó 2012 Published by Elsevier Ltd.
Keywords: Muscle power Parkinson’s disease Motor impairments Muscle strength
1. Introduction The cardinal motor impairments of Parkinson’s disease (PD) are traditionally considered to be bradykinesia, tremor and rigidity. Reduced muscle strength (i.e. reduced maximum force generated, regardless of movement speed) has been identified as an additional motor impairment. It is clear that people with PD lack muscle strength in their lower limbs, particularly in the hip and knee extensors, compared to the general older population [1e3]. This impairment is likely to be due to both the disease process [4e6] as well as to reduced physical activity [7e9]. Reduced muscle strength
* Corresponding author. Movement Disorders Unit, Department of Neurology, University of Sydney, Westmead Hospital, Sydney, Australia. Tel.: þ61 2 9845 6793; fax: þ61 2 9635 6684. E-mail address: [email protected] (V.S.C. Fung). 1353-8020/$ e see front matter Ó 2012 Published by Elsevier Ltd. doi:10.1016/j.parkreldis.2012.05.007
has been shown to contribute to reduced mobility [2,3,10] and falls [11] in people with PD. Muscle power is a measure of the ability to use muscles quickly (i.e. speed force of muscle contraction) and is typically measured across a range of loads from light to very heavy. Muscle power is most commonly measured in the leg extensor muscles, since these large muscles need to be powerful enough to perform everyday weight-bearing activities such as walking, standing up from sitting and stair climbing [12]. In older people, reduced leg muscle power has been shown to be associated with impaired mobility and increased fall risk [12e14]. To date, our group have reported in a sample of forty people with PD that leg extensor muscle power is reduced compared to a control group [1] and that this reduction in muscle power is associated with reduced walking speed and past falls to a greater extent than muscle strength [15]. Given that muscle power is the product of speed and force of muscle contraction, it would be expected that both bradykinesia
S.S. Paul et al. / Parkinsonism and Related Disorders 18 (2012) 974e977
and weakness could potentially contribute to reduced muscle power in people with PD. Previous studies using isokinetic tests reveal that as speed of testing increases, maximum force generated by people with PD diminishes to a greater extent than normal [16e19]. However, the relative contributions of bradykinesia and weakness to muscle power have not been reported. Additionally, there are suggestions that action tremor influences muscle strength in the upper limb [20]. Although this does not appear to be the case in the lower limb [21], it remains unknown whether tremor in the lower limbs may contribute to reduced leg muscle power. It is theoretically possible that rigidity of the lower limb muscles could limit leg muscle power, but this possibility has not been tested. Furthermore, since age and gender are known to influence muscle strength [22], it is expected that these variables will influence muscle power. Therefore, the aim of this study was to determine the relative contribution of the major motor impairments (bradykinesia, tremor, rigidity and muscle weakness) to leg extensor muscle power in people with PD when taking into account age and gender. 2. Methods 2.1. Participants A convenience sample of community-dwelling people with a diagnosis of idiopathic PD was recruited. People with PD who had previously participated in research studies and had agreed to remain on our database for future studies were invited to participate. Participants were also recruited via an advertisement placed in a PD association newsletter. All participants were aged 40 years and were able to walk independently with or without a walking aid. Participants were excluded if they had significant cognitive impairment (Mini-Mental State Examination score < 24) [23], suffered from other neurological conditions (e.g. previous stroke, traumatic brain injury or peripheral neuropathies), orthopaedic conditions (e.g. severe arthritis or joint replacements), or any unstable cardiovascular conditions (e.g. presence of chest pain or recent cardiac surgery) that would interfere with the safety of assessment and/or interpretation of results. We did not exclude participants on the basis of medications taken (e.g. statins or low dose steroids) that are known to influence muscle strength in a small percentage of individuals. Each person was tested when their PD medications were working optimally, usually 1 h after taking their medication. This study was approved by the relevant Human Ethics Committee and all participants gave written informed consent prior to testing. 2.2. Outcome measures Clinical scores for measures of bradykinesia, tremor and rigidity were derived from the Motor (Part 3) section of the Movement Disorders Society-sponsored version of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [24]. Lower limb bradykinesia was scored as the sum of Items 3.7 (toe tapping) and 3.8 (leg agility) for both legs, giving a total score from 0 to 16. Lower limb tremor was scored as the sum of left and right legs for Item 3.17 (rest tremor amplitude), and lower limb rigidity was scored as the sum of left and right legs for Item 3.3 (rigidity) of the MDSUPDRS. The total score for tremor and rigidity was from 0 to 8. Muscle strength and muscle power testing were conducted as per the protocol described previously by our research group [1]. In summary, maximal muscle strength was determined by the one repetition maximum (1RM), which is the maximal load that a person is able to lift once through complete range of motion [25], using a pneumatic variable resistance seated leg press (Keiser A420, Keiser Sports Health Equipment, Fresno CA). The order of testing left and right sides was randomised for each participant. Muscle strength was scored in kg. Leg extensor muscle power of each leg was assessed using the variable resistance equipment at six relative loads (30%e80% of 1RM at 10% increments). The peak power output for each leg was recorded in watts (W). Muscle strength and muscle power values presented are the average of both legs. All tests were conducted in a laboratory during a single assessment session of 2.5 h duration. Tests of mobility and balance were also conducted during this session; these results will be reported separately. 2.3. Statistical analysis Associations between motor impairments, age, gender (explanatory variables) and leg extensor peak muscle power (outcome variable) were examined with univariate linear regression. Each of the explanatory variables (lower limb bradykinesia, tremor, rigidity, leg extensor muscle strength, age and gender) was entered into a multivariate linear regression model. The proportion of variability in peak muscle power explained by the explanatory variables was determined using the R2
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statistic from the multivariate linear regression model. This multivariate linear regression model was also used to determine the relative contribution of each motor impairment, age and gender, to leg extensor peak muscle power. Data were analysed using SPSS version 18 (Chicago IL). Prior to undertaking these analyses, Pearson’s correlation coefficients were calculated to ensure that none of the explanatory variables were too highly correlated to be entered into the same multivariate model. Since all of these correlation coefficients were less than 0.8, each of these explanatory variables was entered into the multivariate model. In order to determine the most appropriate muscle power measure to use as the outcome variable, Pearson’s correlation coefficients were used to assess correlations between muscle power at each of the six relative loads and peak muscle power. Since peak muscle power was found to be highly correlated with muscle power at each of the six relative loads (r values ranged from 0.92 to 0.99), peak power was used as the outcome variable for the statistical analyses.
3. Results Eighty-two people with PD (55 male, 27 female) participated in this study (Table 1). Seventy-six participants were taking levodopa: 27 were taking it in isolation and the remainder was taking it in combination with other medications for PD (dopamine agonists, anticholinergics, MAO-B inhibitors, and COMT inhibitors). Three participants were not taking levodopa, but were taking a dopamine agonist with or without an anticholinergic, while three participants were not taking any PD medications. Eight participants were receiving deep-brain stimulation. This sample of participants with PD had mild to moderate lower limb bradykinesia but only mild lower limb tremor and rigidity (Table 2). Univariate linear regression revealed that low levels of bradykinesia, low levels of rigidity, high levels of muscle strength, younger age and male gender were associated with increased levels of peak leg extensor muscle power (Table 3). The multivariate linear regression model including lower limb bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg extensor muscle power (Table 3). Low levels of lower limb bradykinesia, high levels of leg extensor muscle strength, younger age and male gender were associated with increased levels of peak leg extensor muscle power. Muscle strength had the strongest association with muscle power (b ¼ 0.7), while bradykinesia had only a small association with muscle power (b ¼ 0.1). Tremor and rigidity had negligible association with muscle power (b ¼ 0). Age and male gender each had a small to moderate association with muscle power (b ¼ 0.2 for age, 0.2 for male gender).
4. Discussion This study has shown that reduced muscle strength is the motor impairment that is the greatest contributor to reduced muscle power in people with PD when tested in the “on” state. The dominant contribution of strength is maintained even when cardinal classical Parkinsonian motor impairments, age and gender are considered. Bradykinesia of the lower limbs was shown to be weakly associated with reduced leg extensor muscle power.
Table 1 Participant characteristics (N ¼ 82). Characteristic
Mean (SD)
Range
Age (years) PD duration (years) “On” MDS-UPDRS motor score (0e132) Hoehn & Yahr stage (1e5) MMSE score (0e30)
66.5 7.5 31 2.1 29.2
44e87 0.2e30 8e57 1e4 26e30
(7.6) (5.7) (12) (0.7) (1.0)
PD: Parkinson’s disease. MDS-UPDRS: Movement Disorders Society-sponsored version of the Unified Parkinson’s Disease Rating Scale. MMSE: Mini-mental State Examination.
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S.S. Paul et al. / Parkinsonism and Related Disorders 18 (2012) 974e977
Table 2 Motor impairments and muscle power for the 82 participants.
Lower limb bradykinesia (0e16) Lower limb tremor (0e8) Lower limb rigidity (0e8) Leg extensor muscle strength (kg) Leg extensor peak muscle power (W)
Mean (SD)
Range
6.0 0.3 0.9 86.2 456.2
1e13 0e3 0e4 37.4e179.2 126.0e992.5
(3.0) (0.7) (1.1) (25.5) (165.5)
Tremor and rigidity made no significant contribution to muscle power. Previous studies found that action tremor influenced muscle strength of the upper limb [20,26], but such a relationship does not appear to be present in lower limb muscles [21]. Increased rigidity was associated with reduced muscle power of the leg extensors in the univariate models, but this association was not significant when the other motor impairments, age and gender were entered into the model. It is possible that rigidity in the hip and knee flexors could interfere with fast hip and knee extension, explaining its association with reduced power production of the leg extensors in the univariate model. However, the contribution of rigidity to this active movement is inconsequential when other impairments are considered. As expected, leg muscle power was influenced by age and gender. Our results are consistent with results from the general older population which show reductions in muscle strength and muscle power of the lower limbs [22] due to age-related reductions in muscle volume [27], particularly of fast twitch Type II muscle fibres [28]. Therefore, as people with PD age, loss of leg muscle power is likely to occur not only from the loss of fast twitch muscle fibres associated with ageing, but also from bradykinesia associated with their PD. The association between male gender and increased leg muscle power has also been established by studies in older people showing that men are more powerful than women [22]. The findings of this study are in line with work previously conducted by our research group showing deficits in muscle power even when “on” medication [1,15]. The strength (mean 86.2 SD 25.5 kg) and power (456.2 165.5 W) of the lower limb extensors in the current study are comparable to that previously reported (strength: 90.1 31.2 kg, power: 437.9 186.3 W) to be significantly reduced compared to a control group (strength: 98.8 33.8 kg, power: 561.9 226.0 W) [1]. On average, the strength deficit in PD is approximately 10% while the power deficit is approximately 20%. The larger sample size of the current study has allowed us not only to confirm the significant magnitude of the muscle power deficit in PD, but also to establish strength as the major contributor to leg muscle power in a multivariate linear
regression model including other motor impairments, age and gender. The findings that reduced strength and bradykinesia make significant independent contributions to reduced muscle power in people with PD, even when “on” medication and when age and gender are accounted for, is of clinical significance given that reduced muscle power is associated with increased fall risk and reduced walking speed [15], two major causes of morbidity in PD. Reduced muscle power, reduced muscle strength and bradykinesia are potential targets for therapeutic interventions. Muscle power training has been demonstrated to be a safe and effective intervention for older people [14,29] and warrants investigation in people with PD. Muscle power training has the potential to improve both muscle strength [8] and bradykinesia simultaneously and such training may improve walking ability and reduce fall risk, over and above optimising medical treatment. There were a number of limitations to this study. Due to the nature of the power testing equipment, all participants needed to be able to attend the university laboratory for muscle power testing and so we were unable to recruit people with severe PD. This resulted in a convenience sample of people with mild to moderate PD, not selected on the basis of anti-parkinsonian treatment. Future studies should also include people with more severe PD in order to more firmly establish the associations between cardinal motor impairments and leg muscle power. The clinical rating of bradykinesia using the MDS-UPDRS captures three aspects of akinesia: bradykinesia (reduced speed of movement), akinesia (difficulty initiating movement) and hypokinesia (reduced amplitude of movement). However, muscle power focuses only on a single aspect of akinesia, that of bradykinesia (i.e. reduced speed of movement). It may therefore be that the weak association between bradykinesia and reduced muscle power is due to the inability of the clinical measure to distinguish reduced speed of movement from reduced amplitude of movement and lack of movement initiation [30]. Future studies using more sophisticated quantitative measures of bradykinesia (e.g. accelerometry) and rigidity may further elucidate these relationships. Additionally, funding and logistical constraints did not allow us to test PD participants while “off” medication, so we cannot comment on the contribution of impairments to muscle power in the “off” state. Nevertheless, our results clearly demonstrate that deficits in muscle power and muscle strength as well as bradykinesia are evident even in the “on” state. In summary, this study has shown that reduced leg extensor muscle power in people with PD when tested in the “on” state is associated mostly with reduced muscle strength and to a lesser degree with higher levels of bradykinesia, even when age and
Table 3 Univariate and multivariate associations between motor impairments, age, gender and leg extensor muscle power. P value
Unstandardized b (95% CI)
Univariate models examining associations with leg extensor muscle power Lower limb bradykinesia (0e16) 0.05 Lower limb rigidity (0e8) 0.05 Lower limb tremor (0e8) 0.01 Leg extensor muscle strength (kg) 0.84 Age (years) 0.16 Male gender (yes/no) 0.46
0.03 0.02 0.16 <0.001 <0.001 <0.001
13.2 40.3 35.3 5.94 8.93 239.5
(25.2 to 1.2) (74.2 to 6.4) (14.4 to e85.0) (5.36 to 6.52) (13.3 to 4.5) (182.7 to 296.3)
Multivariate model examining associations with leg extensor muscle power 0.89 Lower limb bradykinesia (0e16) Lower limb rigidity (0e8) Lower limb tremor (0e8) Leg extensor muscle strength (kg) Age (years) Male gender (yes/no)
<0.001 0.03 0.70 0.39 <0.001 <0.001 <0.001
5.07 2.44 7.61 4.53 4.08 79.56
(9.49 to 0.64) (14.90 to 10.02) (25.17 to 9.94) (3.82 to 5.24) (5.83 to 2.34) (43.15 to 115.97)
Explanatory variables
Adjusted R2
Standardized b
0.09 0.02 0.03 0.70 0.19 0.23
S.S. Paul et al. / Parkinsonism and Related Disorders 18 (2012) 974e977
gender are accounted for. Improving leg muscle power may improve walking ability and reduce fall risk, hence leg muscle power training in people with PD warrants investigation as a therapeutic strategy. Acknowledgements This study was supported by a seeding grant from the Physiotherapy Research Foundation of Australia (ID: S10-012). SS Paul receives financial assistance from a National Health and Medical Research Council of Australia (NHMRC) postgraduate scholarship. C Sherrington receives salary funding from the NHMRC. VSC Fung is on advisory boards and/or has received travel grants from Abbott, Allergan, Boehringer-Ingelheim, Hospira, Lundbeck and Novartis. CG Canning has no financial disclosures to make. The authors wish to thank Jooeun Song for her assistance with data collection. We also thank the people with PD who participated in this research. References [1] Allen NE, Canning CG, Sherrington C, Fung VSC. Bradykinesia, muscle weakness and reduced muscle power in Parkinson’s disease. Mov Disord 2009;24: 1344e51. [2] Inkster LM, Eng JJ, MacIntyre DL, Stoessl AJ. Leg muscle strength is reduced in Parkinson’s disease and relates to the ability to rise from a chair. Mov Disord 2003;18:157e62. [3] Paasuke M, Ereline J, Gapeyeva H, Joost K, Mottus K, Taba P. Leg-extension strength and chair-rise performance in elderly women with Parkinson’s disease. J Aging Phys Activ 2004;12:511e24. [4] Pedersen SW, Oberg B. Dynamic strength in Parkinson’s disease. Quantitative measurements following withdrawal of medication. Eur Neurol 1993;33: 97e102. [5] Robichaud JA, Pfann KD, Comella CL, Brandabur M, Corcos DM. Greater impairment of extension movements as compared to flexion movements in Parkinson’s disease. Exp Brain Res 2004;156:240e54. [6] Corcos DM, Chen CM, Quinn NP, McAuley J, Rothwell JC. Strength in Parkinson’s disease: relationship to rate of force generation and clinical status. Ann Neurol 1996;39:79e88. [7] Van Nimwegen M, Speelman AD, Hofman-van Rossum EJM, Overeem S, Deeg DJH, Borm GF, et al. Physical inactivity in Parkinson’s disease. J Neurol 2011;258:2214e21. [8] Falvo MJ, Schilling BK, Earhart GM. Parkinson’s disease and resistive exercise: rationale, review, and recommendations. Mov Disord 2008;23:1e11. [9] Morris ME, Martin CL, Schenkman ML. Striding out with Parkinson disease: evidence-based physical therapy for gait disorders. Phys Ther 2010;90:280e8. [10] Nallegowda M, Singh U, Handa G, Khanna M, Wadhwa S, Yadav SL, et al. Role of sensory input and muscle strength in maintenance of balance, gait, and posture in Parkinson’s disease: a pilot study. Am J Phys Med Rehabil 2004;83: 898e908.
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[11] Latt MD, Lord SR, Morris JGL, Fung VSC. Clinical and physiological assessments for elucidating falls risk in Parkinson’s disease. Mov Disord 2009;24:1280e9. [12] Skelton DA, Kennedy J, Rutherford OM. Explosive power and asymmetry in leg muscle function in frequent fallers and non-fallers aged over 65. Age Ageing 2002;31:119e25. [13] Portegijs E, Sipila S, Pajala S, Lamb SE, Alen M, Kaprio J, et al. Asymmetrical lower extremity power deficit as a risk factor for injurious falls in healthy older women. J Am Geriatr Soc 2006;54:551e3. [14] Orr R, de Vos NJ, Singh NA, Ross DA, Stavrinos TM, Fiatarone-Singh MA. Power training improves balance in healthy older adults. J Gerontol A Biol Sci Med Sci 2006;61A:78e85. [15] Allen NE, Sherrington C, Canning CG, Fung VSC. Reduced muscle power is associated with slower walking velocity and falls in people with Parkinson’s disease. Parkinsonism Relat Disord 2010;16:261e4. [16] Kakinuma S, Nogaki H, Pramanik B, Morimatsu M. Muscle weakness in Parkinson’s disease: isokinetic study of the lower limbs. Eur Neurol 1998;39: 218e22. [17] Nogaki H, Fukusako T, Sasabe F, Negoro K, Morimatsu M. Muscle strength in early Parkinson’s disease. Mov Disord 1995;10:225e6. [18] Nogaki H, Kakinuma S, Morimatsu M. Muscle weakness in Parkinson’s disease: a follow-up study. Parkinsonism Relat Disord 2001;8:57e62. [19] Akima H, Kano Y, Enomoto Y, Ishizu M, Okada M, Oishi Y, et al. Muscle function in 164 men and women aged 20e84 yr. Med Sci Sport Exer 2001;33: 220e6. [20] Brown P, Corcos DM, Rothwell JC. Does parkinsonian action tremor contribute to muscle weakness in Parkinson’s disease? Brain 1997;120:401e8. [21] Vaillancourt DE, Prodoehl J, Sturman MM, Bakay RA, Metman LV, Corcos DM. Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson’s disease. Mov Disord 2006;21:50e8. [22] Samson MM, Meeuwsen IBAE, Crowe A, Dessens JAG, Duursma SA, Verhaar HJJ. Relationships between physical performance measures, age, height, and body weight in healthy adults. Age Ageing 2000;29:235e42. [23] Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975; 12:189e98. [24] Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008;23:2129e70. [25] Sale DG. Testing strength and power. In: MacDougall JD, Wenger HA, Green HJ, editors. Physiological testing of the high-performance athlete. 2nd ed. Champaign, IL: Human Kinetic Books; 1991. p. 21e106. [26] Brown P, Corcos DM, Rothwell JC. Action tremor and weakness in Parkinson’s disease: a study of the elbow extensors. Mov Disord 1998;13:56e60. [27] Lexell J, Taylor CC, Sjostrom M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci 1988;84:275e94. [28] Lexell J, Downham D. What is the effect of ageing on type 2 muscle fibres? J Neurol Sci 1992;107:250e1. [29] Henwood TR, Riek S, Taaffe DR. Strength versus muscle power-specific resistance training in community-dwelling older adults. J Gerontol A Biol Sci Med Sci 2008;63A:83e91. [30] Heldman DA, Giuffrida JP, Chen R, Payne M, Mazzella F, Duker AP, et al. The modified bradykinesia rating scale for Parkinson’s disease: reliability and comparison with kinematic measures. Mov Disord 2011;26:1859e63.
Contents lists available at SciVerse ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson’s disease S.S. Paul a, C.G. Canning a, C. Sherrington b, V.S.C. Fung c, d, * a
Clinical & Rehabilitation Sciences Research Group, Faculty of Health Sciences, University of Sydney, Sydney, Australia Musculoskeletal Division, The George Institute for Global Health, University of Sydney, Sydney, Australia c Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia d Sydney Medical School, University of Sydney, Sydney, Australia b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 23 February 2012 Received in revised form 17 April 2012 Accepted 3 May 2012
Background: Reduced muscle power (speed strength) is associated with increased fall risk and reduced walking speed in people with Parkinson’s disease (PD) as well as in the general older population. This study aimed to determine the relative contribution of motor impairments (bradykinesia, tremor, rigidity and weakness) to reduced leg muscle power in people with PD. Methods: Eighty-two people with PD were tested while “on” medication. Leg extensor muscle strength and muscle power were measured using pneumatic variable resistance equipment. Lower limb bradykinesia, rigidity and tremor were measured using the Movement Disorders Society-sponsored Unified Parkinson’s Disease Rating Scale. Associations between motor impairments and leg muscle power were examined using linear regression. Results: Univariate models revealed that muscle strength (R2 ¼ 0.84), bradykinesia (R2 ¼ 0.05) and rigidity (R2 ¼ 0.05) were significantly associated with leg muscle power, while tremor was not. A multivariate model including bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg muscle power. This model revealed reduced muscle strength to be the major determinant of reduced muscle power (b ¼ 0.7), while bradykinesia was a minor contributor to reduced muscle power (b ¼ 0.1), even when accounting for age and gender. Conclusions: The findings that reduced strength and bradykinesia contribute to reduced muscle power in people with PD tested “on” medication suggest that these impairments are potential targets for physical interventions. Ó 2012 Published by Elsevier Ltd.
Keywords: Muscle power Parkinson’s disease Motor impairments Muscle strength
1. Introduction The cardinal motor impairments of Parkinson’s disease (PD) are traditionally considered to be bradykinesia, tremor and rigidity. Reduced muscle strength (i.e. reduced maximum force generated, regardless of movement speed) has been identified as an additional motor impairment. It is clear that people with PD lack muscle strength in their lower limbs, particularly in the hip and knee extensors, compared to the general older population [1e3]. This impairment is likely to be due to both the disease process [4e6] as well as to reduced physical activity [7e9]. Reduced muscle strength
* Corresponding author. Movement Disorders Unit, Department of Neurology, University of Sydney, Westmead Hospital, Sydney, Australia. Tel.: þ61 2 9845 6793; fax: þ61 2 9635 6684. E-mail address: [email protected] (V.S.C. Fung). 1353-8020/$ e see front matter Ó 2012 Published by Elsevier Ltd. doi:10.1016/j.parkreldis.2012.05.007
has been shown to contribute to reduced mobility [2,3,10] and falls [11] in people with PD. Muscle power is a measure of the ability to use muscles quickly (i.e. speed force of muscle contraction) and is typically measured across a range of loads from light to very heavy. Muscle power is most commonly measured in the leg extensor muscles, since these large muscles need to be powerful enough to perform everyday weight-bearing activities such as walking, standing up from sitting and stair climbing [12]. In older people, reduced leg muscle power has been shown to be associated with impaired mobility and increased fall risk [12e14]. To date, our group have reported in a sample of forty people with PD that leg extensor muscle power is reduced compared to a control group [1] and that this reduction in muscle power is associated with reduced walking speed and past falls to a greater extent than muscle strength [15]. Given that muscle power is the product of speed and force of muscle contraction, it would be expected that both bradykinesia
S.S. Paul et al. / Parkinsonism and Related Disorders 18 (2012) 974e977
and weakness could potentially contribute to reduced muscle power in people with PD. Previous studies using isokinetic tests reveal that as speed of testing increases, maximum force generated by people with PD diminishes to a greater extent than normal [16e19]. However, the relative contributions of bradykinesia and weakness to muscle power have not been reported. Additionally, there are suggestions that action tremor influences muscle strength in the upper limb [20]. Although this does not appear to be the case in the lower limb [21], it remains unknown whether tremor in the lower limbs may contribute to reduced leg muscle power. It is theoretically possible that rigidity of the lower limb muscles could limit leg muscle power, but this possibility has not been tested. Furthermore, since age and gender are known to influence muscle strength [22], it is expected that these variables will influence muscle power. Therefore, the aim of this study was to determine the relative contribution of the major motor impairments (bradykinesia, tremor, rigidity and muscle weakness) to leg extensor muscle power in people with PD when taking into account age and gender. 2. Methods 2.1. Participants A convenience sample of community-dwelling people with a diagnosis of idiopathic PD was recruited. People with PD who had previously participated in research studies and had agreed to remain on our database for future studies were invited to participate. Participants were also recruited via an advertisement placed in a PD association newsletter. All participants were aged 40 years and were able to walk independently with or without a walking aid. Participants were excluded if they had significant cognitive impairment (Mini-Mental State Examination score < 24) [23], suffered from other neurological conditions (e.g. previous stroke, traumatic brain injury or peripheral neuropathies), orthopaedic conditions (e.g. severe arthritis or joint replacements), or any unstable cardiovascular conditions (e.g. presence of chest pain or recent cardiac surgery) that would interfere with the safety of assessment and/or interpretation of results. We did not exclude participants on the basis of medications taken (e.g. statins or low dose steroids) that are known to influence muscle strength in a small percentage of individuals. Each person was tested when their PD medications were working optimally, usually 1 h after taking their medication. This study was approved by the relevant Human Ethics Committee and all participants gave written informed consent prior to testing. 2.2. Outcome measures Clinical scores for measures of bradykinesia, tremor and rigidity were derived from the Motor (Part 3) section of the Movement Disorders Society-sponsored version of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) [24]. Lower limb bradykinesia was scored as the sum of Items 3.7 (toe tapping) and 3.8 (leg agility) for both legs, giving a total score from 0 to 16. Lower limb tremor was scored as the sum of left and right legs for Item 3.17 (rest tremor amplitude), and lower limb rigidity was scored as the sum of left and right legs for Item 3.3 (rigidity) of the MDSUPDRS. The total score for tremor and rigidity was from 0 to 8. Muscle strength and muscle power testing were conducted as per the protocol described previously by our research group [1]. In summary, maximal muscle strength was determined by the one repetition maximum (1RM), which is the maximal load that a person is able to lift once through complete range of motion [25], using a pneumatic variable resistance seated leg press (Keiser A420, Keiser Sports Health Equipment, Fresno CA). The order of testing left and right sides was randomised for each participant. Muscle strength was scored in kg. Leg extensor muscle power of each leg was assessed using the variable resistance equipment at six relative loads (30%e80% of 1RM at 10% increments). The peak power output for each leg was recorded in watts (W). Muscle strength and muscle power values presented are the average of both legs. All tests were conducted in a laboratory during a single assessment session of 2.5 h duration. Tests of mobility and balance were also conducted during this session; these results will be reported separately. 2.3. Statistical analysis Associations between motor impairments, age, gender (explanatory variables) and leg extensor peak muscle power (outcome variable) were examined with univariate linear regression. Each of the explanatory variables (lower limb bradykinesia, tremor, rigidity, leg extensor muscle strength, age and gender) was entered into a multivariate linear regression model. The proportion of variability in peak muscle power explained by the explanatory variables was determined using the R2
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statistic from the multivariate linear regression model. This multivariate linear regression model was also used to determine the relative contribution of each motor impairment, age and gender, to leg extensor peak muscle power. Data were analysed using SPSS version 18 (Chicago IL). Prior to undertaking these analyses, Pearson’s correlation coefficients were calculated to ensure that none of the explanatory variables were too highly correlated to be entered into the same multivariate model. Since all of these correlation coefficients were less than 0.8, each of these explanatory variables was entered into the multivariate model. In order to determine the most appropriate muscle power measure to use as the outcome variable, Pearson’s correlation coefficients were used to assess correlations between muscle power at each of the six relative loads and peak muscle power. Since peak muscle power was found to be highly correlated with muscle power at each of the six relative loads (r values ranged from 0.92 to 0.99), peak power was used as the outcome variable for the statistical analyses.
3. Results Eighty-two people with PD (55 male, 27 female) participated in this study (Table 1). Seventy-six participants were taking levodopa: 27 were taking it in isolation and the remainder was taking it in combination with other medications for PD (dopamine agonists, anticholinergics, MAO-B inhibitors, and COMT inhibitors). Three participants were not taking levodopa, but were taking a dopamine agonist with or without an anticholinergic, while three participants were not taking any PD medications. Eight participants were receiving deep-brain stimulation. This sample of participants with PD had mild to moderate lower limb bradykinesia but only mild lower limb tremor and rigidity (Table 2). Univariate linear regression revealed that low levels of bradykinesia, low levels of rigidity, high levels of muscle strength, younger age and male gender were associated with increased levels of peak leg extensor muscle power (Table 3). The multivariate linear regression model including lower limb bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg extensor muscle power (Table 3). Low levels of lower limb bradykinesia, high levels of leg extensor muscle strength, younger age and male gender were associated with increased levels of peak leg extensor muscle power. Muscle strength had the strongest association with muscle power (b ¼ 0.7), while bradykinesia had only a small association with muscle power (b ¼ 0.1). Tremor and rigidity had negligible association with muscle power (b ¼ 0). Age and male gender each had a small to moderate association with muscle power (b ¼ 0.2 for age, 0.2 for male gender).
4. Discussion This study has shown that reduced muscle strength is the motor impairment that is the greatest contributor to reduced muscle power in people with PD when tested in the “on” state. The dominant contribution of strength is maintained even when cardinal classical Parkinsonian motor impairments, age and gender are considered. Bradykinesia of the lower limbs was shown to be weakly associated with reduced leg extensor muscle power.
Table 1 Participant characteristics (N ¼ 82). Characteristic
Mean (SD)
Range
Age (years) PD duration (years) “On” MDS-UPDRS motor score (0e132) Hoehn & Yahr stage (1e5) MMSE score (0e30)
66.5 7.5 31 2.1 29.2
44e87 0.2e30 8e57 1e4 26e30
(7.6) (5.7) (12) (0.7) (1.0)
PD: Parkinson’s disease. MDS-UPDRS: Movement Disorders Society-sponsored version of the Unified Parkinson’s Disease Rating Scale. MMSE: Mini-mental State Examination.
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Table 2 Motor impairments and muscle power for the 82 participants.
Lower limb bradykinesia (0e16) Lower limb tremor (0e8) Lower limb rigidity (0e8) Leg extensor muscle strength (kg) Leg extensor peak muscle power (W)
Mean (SD)
Range
6.0 0.3 0.9 86.2 456.2
1e13 0e3 0e4 37.4e179.2 126.0e992.5
(3.0) (0.7) (1.1) (25.5) (165.5)
Tremor and rigidity made no significant contribution to muscle power. Previous studies found that action tremor influenced muscle strength of the upper limb [20,26], but such a relationship does not appear to be present in lower limb muscles [21]. Increased rigidity was associated with reduced muscle power of the leg extensors in the univariate models, but this association was not significant when the other motor impairments, age and gender were entered into the model. It is possible that rigidity in the hip and knee flexors could interfere with fast hip and knee extension, explaining its association with reduced power production of the leg extensors in the univariate model. However, the contribution of rigidity to this active movement is inconsequential when other impairments are considered. As expected, leg muscle power was influenced by age and gender. Our results are consistent with results from the general older population which show reductions in muscle strength and muscle power of the lower limbs [22] due to age-related reductions in muscle volume [27], particularly of fast twitch Type II muscle fibres [28]. Therefore, as people with PD age, loss of leg muscle power is likely to occur not only from the loss of fast twitch muscle fibres associated with ageing, but also from bradykinesia associated with their PD. The association between male gender and increased leg muscle power has also been established by studies in older people showing that men are more powerful than women [22]. The findings of this study are in line with work previously conducted by our research group showing deficits in muscle power even when “on” medication [1,15]. The strength (mean 86.2 SD 25.5 kg) and power (456.2 165.5 W) of the lower limb extensors in the current study are comparable to that previously reported (strength: 90.1 31.2 kg, power: 437.9 186.3 W) to be significantly reduced compared to a control group (strength: 98.8 33.8 kg, power: 561.9 226.0 W) [1]. On average, the strength deficit in PD is approximately 10% while the power deficit is approximately 20%. The larger sample size of the current study has allowed us not only to confirm the significant magnitude of the muscle power deficit in PD, but also to establish strength as the major contributor to leg muscle power in a multivariate linear
regression model including other motor impairments, age and gender. The findings that reduced strength and bradykinesia make significant independent contributions to reduced muscle power in people with PD, even when “on” medication and when age and gender are accounted for, is of clinical significance given that reduced muscle power is associated with increased fall risk and reduced walking speed [15], two major causes of morbidity in PD. Reduced muscle power, reduced muscle strength and bradykinesia are potential targets for therapeutic interventions. Muscle power training has been demonstrated to be a safe and effective intervention for older people [14,29] and warrants investigation in people with PD. Muscle power training has the potential to improve both muscle strength [8] and bradykinesia simultaneously and such training may improve walking ability and reduce fall risk, over and above optimising medical treatment. There were a number of limitations to this study. Due to the nature of the power testing equipment, all participants needed to be able to attend the university laboratory for muscle power testing and so we were unable to recruit people with severe PD. This resulted in a convenience sample of people with mild to moderate PD, not selected on the basis of anti-parkinsonian treatment. Future studies should also include people with more severe PD in order to more firmly establish the associations between cardinal motor impairments and leg muscle power. The clinical rating of bradykinesia using the MDS-UPDRS captures three aspects of akinesia: bradykinesia (reduced speed of movement), akinesia (difficulty initiating movement) and hypokinesia (reduced amplitude of movement). However, muscle power focuses only on a single aspect of akinesia, that of bradykinesia (i.e. reduced speed of movement). It may therefore be that the weak association between bradykinesia and reduced muscle power is due to the inability of the clinical measure to distinguish reduced speed of movement from reduced amplitude of movement and lack of movement initiation [30]. Future studies using more sophisticated quantitative measures of bradykinesia (e.g. accelerometry) and rigidity may further elucidate these relationships. Additionally, funding and logistical constraints did not allow us to test PD participants while “off” medication, so we cannot comment on the contribution of impairments to muscle power in the “off” state. Nevertheless, our results clearly demonstrate that deficits in muscle power and muscle strength as well as bradykinesia are evident even in the “on” state. In summary, this study has shown that reduced leg extensor muscle power in people with PD when tested in the “on” state is associated mostly with reduced muscle strength and to a lesser degree with higher levels of bradykinesia, even when age and
Table 3 Univariate and multivariate associations between motor impairments, age, gender and leg extensor muscle power. P value
Unstandardized b (95% CI)
Univariate models examining associations with leg extensor muscle power Lower limb bradykinesia (0e16) 0.05 Lower limb rigidity (0e8) 0.05 Lower limb tremor (0e8) 0.01 Leg extensor muscle strength (kg) 0.84 Age (years) 0.16 Male gender (yes/no) 0.46
0.03 0.02 0.16 <0.001 <0.001 <0.001
13.2 40.3 35.3 5.94 8.93 239.5
(25.2 to 1.2) (74.2 to 6.4) (14.4 to e85.0) (5.36 to 6.52) (13.3 to 4.5) (182.7 to 296.3)
Multivariate model examining associations with leg extensor muscle power 0.89 Lower limb bradykinesia (0e16) Lower limb rigidity (0e8) Lower limb tremor (0e8) Leg extensor muscle strength (kg) Age (years) Male gender (yes/no)
<0.001 0.03 0.70 0.39 <0.001 <0.001 <0.001
5.07 2.44 7.61 4.53 4.08 79.56
(9.49 to 0.64) (14.90 to 10.02) (25.17 to 9.94) (3.82 to 5.24) (5.83 to 2.34) (43.15 to 115.97)
Explanatory variables
Adjusted R2
Standardized b
0.09 0.02 0.03 0.70 0.19 0.23
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gender are accounted for. Improving leg muscle power may improve walking ability and reduce fall risk, hence leg muscle power training in people with PD warrants investigation as a therapeutic strategy. Acknowledgements This study was supported by a seeding grant from the Physiotherapy Research Foundation of Australia (ID: S10-012). SS Paul receives financial assistance from a National Health and Medical Research Council of Australia (NHMRC) postgraduate scholarship. C Sherrington receives salary funding from the NHMRC. VSC Fung is on advisory boards and/or has received travel grants from Abbott, Allergan, Boehringer-Ingelheim, Hospira, Lundbeck and Novartis. CG Canning has no financial disclosures to make. The authors wish to thank Jooeun Song for her assistance with data collection. We also thank the people with PD who participated in this research. References [1] Allen NE, Canning CG, Sherrington C, Fung VSC. Bradykinesia, muscle weakness and reduced muscle power in Parkinson’s disease. Mov Disord 2009;24: 1344e51. [2] Inkster LM, Eng JJ, MacIntyre DL, Stoessl AJ. Leg muscle strength is reduced in Parkinson’s disease and relates to the ability to rise from a chair. Mov Disord 2003;18:157e62. [3] Paasuke M, Ereline J, Gapeyeva H, Joost K, Mottus K, Taba P. Leg-extension strength and chair-rise performance in elderly women with Parkinson’s disease. J Aging Phys Activ 2004;12:511e24. [4] Pedersen SW, Oberg B. Dynamic strength in Parkinson’s disease. Quantitative measurements following withdrawal of medication. Eur Neurol 1993;33: 97e102. [5] Robichaud JA, Pfann KD, Comella CL, Brandabur M, Corcos DM. Greater impairment of extension movements as compared to flexion movements in Parkinson’s disease. Exp Brain Res 2004;156:240e54. [6] Corcos DM, Chen CM, Quinn NP, McAuley J, Rothwell JC. Strength in Parkinson’s disease: relationship to rate of force generation and clinical status. Ann Neurol 1996;39:79e88. [7] Van Nimwegen M, Speelman AD, Hofman-van Rossum EJM, Overeem S, Deeg DJH, Borm GF, et al. Physical inactivity in Parkinson’s disease. J Neurol 2011;258:2214e21. [8] Falvo MJ, Schilling BK, Earhart GM. Parkinson’s disease and resistive exercise: rationale, review, and recommendations. Mov Disord 2008;23:1e11. [9] Morris ME, Martin CL, Schenkman ML. Striding out with Parkinson disease: evidence-based physical therapy for gait disorders. Phys Ther 2010;90:280e8. [10] Nallegowda M, Singh U, Handa G, Khanna M, Wadhwa S, Yadav SL, et al. Role of sensory input and muscle strength in maintenance of balance, gait, and posture in Parkinson’s disease: a pilot study. Am J Phys Med Rehabil 2004;83: 898e908.
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[11] Latt MD, Lord SR, Morris JGL, Fung VSC. Clinical and physiological assessments for elucidating falls risk in Parkinson’s disease. Mov Disord 2009;24:1280e9. [12] Skelton DA, Kennedy J, Rutherford OM. Explosive power and asymmetry in leg muscle function in frequent fallers and non-fallers aged over 65. Age Ageing 2002;31:119e25. [13] Portegijs E, Sipila S, Pajala S, Lamb SE, Alen M, Kaprio J, et al. Asymmetrical lower extremity power deficit as a risk factor for injurious falls in healthy older women. J Am Geriatr Soc 2006;54:551e3. [14] Orr R, de Vos NJ, Singh NA, Ross DA, Stavrinos TM, Fiatarone-Singh MA. Power training improves balance in healthy older adults. J Gerontol A Biol Sci Med Sci 2006;61A:78e85. [15] Allen NE, Sherrington C, Canning CG, Fung VSC. Reduced muscle power is associated with slower walking velocity and falls in people with Parkinson’s disease. Parkinsonism Relat Disord 2010;16:261e4. [16] Kakinuma S, Nogaki H, Pramanik B, Morimatsu M. Muscle weakness in Parkinson’s disease: isokinetic study of the lower limbs. Eur Neurol 1998;39: 218e22. [17] Nogaki H, Fukusako T, Sasabe F, Negoro K, Morimatsu M. Muscle strength in early Parkinson’s disease. Mov Disord 1995;10:225e6. [18] Nogaki H, Kakinuma S, Morimatsu M. Muscle weakness in Parkinson’s disease: a follow-up study. Parkinsonism Relat Disord 2001;8:57e62. [19] Akima H, Kano Y, Enomoto Y, Ishizu M, Okada M, Oishi Y, et al. Muscle function in 164 men and women aged 20e84 yr. Med Sci Sport Exer 2001;33: 220e6. [20] Brown P, Corcos DM, Rothwell JC. Does parkinsonian action tremor contribute to muscle weakness in Parkinson’s disease? Brain 1997;120:401e8. [21] Vaillancourt DE, Prodoehl J, Sturman MM, Bakay RA, Metman LV, Corcos DM. Effects of deep brain stimulation and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson’s disease. Mov Disord 2006;21:50e8. [22] Samson MM, Meeuwsen IBAE, Crowe A, Dessens JAG, Duursma SA, Verhaar HJJ. Relationships between physical performance measures, age, height, and body weight in healthy adults. Age Ageing 2000;29:235e42. [23] Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 1975; 12:189e98. [24] Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 2008;23:2129e70. [25] Sale DG. Testing strength and power. In: MacDougall JD, Wenger HA, Green HJ, editors. Physiological testing of the high-performance athlete. 2nd ed. Champaign, IL: Human Kinetic Books; 1991. p. 21e106. [26] Brown P, Corcos DM, Rothwell JC. Action tremor and weakness in Parkinson’s disease: a study of the elbow extensors. Mov Disord 1998;13:56e60. [27] Lexell J, Taylor CC, Sjostrom M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci 1988;84:275e94. [28] Lexell J, Downham D. What is the effect of ageing on type 2 muscle fibres? J Neurol Sci 1992;107:250e1. [29] Henwood TR, Riek S, Taaffe DR. Strength versus muscle power-specific resistance training in community-dwelling older adults. J Gerontol A Biol Sci Med Sci 2008;63A:83e91. [30] Heldman DA, Giuffrida JP, Chen R, Payne M, Mazzella F, Duker AP, et al. The modified bradykinesia rating scale for Parkinson’s disease: reliability and comparison with kinematic measures. Mov Disord 2011;26:1859e63.