Physiotherapy versus placebo or no intervention in Parkinson's disease

Claire L Tomlinson; Smitaa Patel; Charmaine Meek; Clare P Herd; Carl E Clarke; Rebecca Stowe; Laila Shah; Catherine M Sackley; Katherine HO Deane; Keith Wheatley; Natalie Ives

doi:10.1002/14651858.CD002817.pub4

. 2013 Sep 10;2013(9):CD002817. doi: 10.1002/14651858.CD002817.pub4

Physiotherapy versus placebo or no intervention in Parkinson's disease

Claire L Tomlinson ^1,^✉, Smitaa Patel ¹, Charmaine Meek ², Clare P Herd ³, Carl E Clarke ³, Rebecca Stowe ¹, Laila Shah ¹, Catherine M Sackley ⁴, Katherine HO Deane ⁵, Keith Wheatley ⁶, Natalie Ives ¹

Editor: Cochrane Movement Disorders Group

PMCID: PMC7120224 PMID: 24018704

Abstract

Background

Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well‐being, thereby enhancing quality of life.

Objectives

To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD.

Search methods

We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012.

Selection criteria

Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD.

Data collection and analysis

Two review authors independently extracted data from each article. We used standard meta‐analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions.

Main results

We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two‐ or six‐minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (‐1.41, 95% CI ‐2.63 to ‐0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (‐0.63 s, 95% CI ‐1.05 to ‐0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician‐rated disability using the Unified Parkinson’s Disease Rating Scale (UPDRS) (total ‐6.15 points, 95% CI‐8.57 to ‐3.73, P < 0.00001; activities of daily living: ‐1.36, 95% CI ‐2.41 to ‐0.30, P = 0.01; and motor: ‐5.01, 95% CI ‐6.30 to ‐3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: ‐1.91 points, 95% CI ‐4.76 to 0.94, P = 0.19) or patient‐rated quality of life (PDQ‐39 Summary Index: ‐0.38 points, 95% CI ‐2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed.

Authors' conclusions

Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two‐ or six‐minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician‐rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.

This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well‐designed randomised controlled trials undertaken to demonstrate the longer‐term efficacy and cost‐effectiveness of 'best practice' physiotherapy in PD.

Plain language summary

Physiotherapy for treatment of Parkinson's disease

In spite of various medical and surgical treatments for Parkinson's disease (PD), patients gradually develop significant physical problems. Physiotherapists aim to enable people with PD to maintain their maximum level of mobility, activity, and independence by monitoring their condition and targeting appropriate treatment. A range of approaches to movement rehabilitation are used, which aim to enhance quality of life by maximising physical ability and minimising problems related to Parkinson's over the whole course of the disease.

Only randomised controlled trials were included in this review. In these studies,a group of participants were given physiotherapy intervention and were compared with another group of participants, who did not receive physiotherapy. Participants were assigned to a group in random fashion so a fair test was established. Thirty‐nine randomised trials involving 1827 participants were identified as suitable for this review. The quality of the trials was not high because in many, methods were not reported adequately and blinding was not feasible. These trials assessed various physiotherapy interventions, so the trials were grouped according to the type of intervention being used (i.e. general physiotherapy, exercise, treadmill training, cueing, dance, or martial arts).

Improvement in all walking outcomes (except the 10‐ or 20‐metre walk test) was noted with physiotherapy intervention. However, these improvements were significant only for walking speed, walking endurance, and freezing of gait. Mobility and balance also improved with a physiotherapy intervention, with significant improvements reported in one test of mobility (the Timed Up & Go test, which times how long it takes a person to get up from a chair, walk a certain distance, then walk back to the chair and sit down) and in two tests of balance (one assessing how far a person can reach before he or she loses balance (Functional Reach Test) and another assessing multiple aspects of balance (Berg Balance Scale)). Clinician‐rated disability, using the Unified Parkinson’s Disease Rating Scale (UPDRS), was also improved with physiotherapy intervention. No difference was observed between the two groups in falls or patient‐rated quality of life. One study reported that adverse events were rare; no other studies reported data on this outcome. When the different physiotherapy interventions were compared, no evidence suggested that treatment effect differed across the physiotherapy interventions for any of the outcomes assessed.

This review provides evidence of the short‐term benefit of physiotherapy for the treatment of PD. Although most observed differences were small, improvements in walking speed, balance with the Berg Balance Scale, and clinician‐rated disability using the UPDRS were of a size that patients may consider them to be important. These benefits should be interpreted with caution because of the quality of the included trials, and the lack of common assessment of treatment effects. This affected the quantity of data that we could use for analysis.

Background

Parkinson’s disease (PD) is a complex neurodegenerative disorder (Rubenis 2007) with wide reaching implications for patients and their families. Although disability can occur at all stages of the disease (Deane 2001a), PD is progressive in nature, and so patients face increased difficulties with activities of daily living (ADL) (Kwakkel 2007) and various aspects of mobility such as gait, transfers, balance, and posture (Keus 2007b). Ultimately, this leads to decreased independence, inactivity, and social isolation (Keus 2007b), resulting in reduced quality of life (Schrag 2000).

The management of PD has traditionally centred on drug therapy, with levodopa viewed as the 'gold standard' treatment (Rascol 2002). However, even with optimal medical management, patients with PD experience deterioration in body function, daily activities, and participation (Nijkrake 2007). For this reason, support has been increasing for the inclusion of rehabilitation therapies as an adjuvant to pharmacological and neurosurgical treatment (Gage 2004; Nijkrake 2007), and a call for the move towards multidisciplinary management of this multidimensional condition (Robertson 2003; Rubenis 2007).

The physiotherapist is a member within this multidisciplinary team (Robertson 2008; Rubenis 2007), whose purpose is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person (Plant 2000; Deane 2001a). Physiotherapy for PD focuses on transfers, posture, upper limb function, balance (and falls), gait, and physical capacity and (in)activity by using cueing strategies, cognitive movement strategies, and exercise to optimise the patient’s independence, safety, and well‐being, thereby enhancing quality of life (Keus 2004; Keus 2007a).

Referral rates to physiotherapy for people with PD have historically been low (Mutch 1986; Yarrow 1999). However, in recent years, the number of referrals has increased, with a survey by Parkinson’s UK in 2008 reporting that 54% of the 13,000 members surveyed had seen a physiotherapist compared with 27% in a survey undertaken in 1998 (PDS 2008; Yarrow 1999). This rise in referrals may be attributed to two factors. First, guidelines published by the National Collaborating Centre for Chronic Conditions (Nat Collab Centre for Chronic Conditions 2006) recommended that physiotherapy be made available throughout all stages of the disease, raising the profile of the profession. This has been further supported by the publication of Dutch physiotherapy guidelines (Keus 2004), which provide specific information for physiotherapists involved in the management of PD. Second, a substantial increase has been noted in the number of trials completed over the past decade (particularly in the last five years), offering supportive evidence for the inclusion of physiotherapy in the management of PD (Keus 2009).

This Cochrane review assessing the effectiveness of physiotherapy intervention versus no physiotherapy intervention in patients with PD was first published in 2001, and included only 11 randomised controlled trials with a total of 280 participants (Deane 2001a). Most of the trials in the review reported a positive effect in favour of physiotherapy, but few outcome measures were statistically significant. This, combined with the presence of methodological flaws, small sample sizes, and the possibility of publication bias, led Deane et al. to conclude that evidence was insufficient to support or refute the efficacy of physiotherapy for PD (Deane 2001a). This review updates the previous Cochrane review. We appraised and synthesised relevant randomised controlled trials, and we conducted a meta‐analysis of outcomes where possible.

Objectives

To compare the effectiveness of physiotherapy intervention versus no physiotherapy intervention in participants with PD.

To indirectly compare the different physiotherapy interventions used within the various trials.

Methods

Criteria for considering studies for this review

Types of studies

For inclusion in the review, we considered all randomised controlled trials (including the first phase of cross‐over trials) comparing a physiotherapy intervention with no physiotherapy intervention (including placebo control). We included trials in which the no intervention arm used an active or credible placebo, as long as no physiotherapy was delivered to this group. We included only trials that implemented random methods of treatment allocation.

Types of participants

Participants with a diagnosis of PD (as defined by the authors of the studies):

Any duration of PD.
All ages.
Any drug therapy.
Any duration of physiotherapy treatment.

Types of interventions

Physiotherapy interventions aim to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. Physiotherapy encompasses a wide range of techniques, so we were inclusive in our definition of physiotherapy interventions (including those not delivered by a physiotherapist) with trials of general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts included.

Types of outcome measures

Gait outcomes such as:

Two‐ or six‐minute walk test (m) － measures the number of metres a person can walk in two or six minutes, thereby providing a measurement of walking endurance (Kersten 2004).
Walking speed

- 10‐ or 20‐metre walk test (s) － measures the time in seconds that a person takes to walk 10 or 20 metres, thereby providing a measurement of gait speed (Kersten 2004).
- Speed (m/s) － measures the rate of change of position, recorded in metres per second (Trew 2005).

Cadence (steps/min) － measures the number of steps taken in a given period, which is then converted into the number of steps taken per minute (Trew 2005).
Stride length (m) － measures the average distance (in metres) between two successive placements of the same foot (Whittle 1996).
Step length (m) － measures the average distance (in metres) between successive foot‐to‐floor contacts with opposite feet (Trew 2005).
Freezing of Gait Questionnaire － validated questionnaire for the assessment of freezing of gait. The questionnaire consists of six items, and scores range from 0 to 24, with higher scores corresponding to more severe freezing of gait (Giladi 2000).

Functional mobility and balance outcomes such as:

Timed Up & Go (s) － measures time taken in seconds for a person to get up from a chair, walk a certain distance (usually three metres), turn around, and walk back to the chair and sit down (Podsiadlo 1991).
Functional Reach Test (cm) － “the maximal distance one can reach forward beyond arm’s length, while maintaining a fixed base of support in the standing position” (Duncan 1990).
Berg Balance Scale － validated questionnaire designed to measure functional standing balance of the older adult. The measure consists of 14 items, and scores range from 0 to 56, with 0 to 20 = high fall risk; 21 to 40 = medium fall risk; and 41 to 56 = low fall risk (Berg 1992; Qutubuddin 2005).
Activity Specific Balance Confidence － 16‐item self‐report questionnaire that asks individuals to rate their confidence that they will maintain their balance in the course of daily activities. Each item is rated from 0% (no confidence) to 100% (complete confidence) (Powell 1995; Talley 2008).

Data on falls such as:

Number of patients falling － e.g. falls diary.
Falls Efficacy Scale － 10‐item patient‐reported questionnaire that measures how confident a person is at carrying out various activities of daily living (ADL). Items are rated from 1 to 10, with higher scores correlating with lower levels of confidence, and a total score of 70 or higher indicating that a person has a fear of falling (Tinetti 1990).
Falls Efficacy Scale International － 16‐item questionnaire that includes the 10 original items of the standard Falls Efficacy Scale, as well as six items regarding higher functioning and social activities. Each item is rated on a scale of 1 to 4, with 1 being ‘not concerned at all’ and 4 ‘very concerned’ (maximum score out of 64) (Yardley 2005).

Clinician‐rated impairment and disability measures such as:

Hoehn & Yahr － scale used to describe how symptoms of Parkinson's disease progress. Scale ranges from 0 to 5, with higher levels indicating greater disability (Hoehn 1967).
Unified Parkinson's Disease Rating Scale (UPDRS) － designed to assess motor impairment and disability in Parkinson’s disease. Higher scores correspond to greater disability (Fahn 1987).

- Total － scores range from 0 to 176.
- Mental － scores range from 0 to 16.
- ADL － scores range from 0 to 52.
- Motor － scores range from 0 to 108.

Webster Rating Scale － assessment of severity of disease and clinical impairment against 10 items using a scale of 0=normal to 3=maximum impairment: bradykinesia, rigidity, posture, upper extremity swing, gait, tremor at rest, facial expression, seborrhoea, speech, and self care. Scores range from 0 to 30, with higher scores indicating greater disease severity and disability (Webster 1968).
Columbia University Rating Scale － assessment of motor impairment and activities of daily living against 13 items, using a five‐point scale for each to yield a total score between 0=normal and 65=maximum disability (Yahr 1969).

Patient‐rated quality of life such as:

Parkinson's Disease Questionnaire39 (PDQ‐39) － PD‐specific health‐related quality of life questionnaire containing 39 items divided among eight domains. Scores range from 0 to 100, with higher scores corresponding to poorer quality of life (Jenkinson 1997; Peto 1995).
PDQUALIF － PD‐specific health‐related quality of life questionnaire containing 32 items in seven dimensions and one item of global health‐related quality of life. Total score ranges from 0 to 128, with higher scores indicating poorer quality of life (Welsh 2003).
PDQL － PD‐specific health‐related quality of life questionnaire containing 37 items grouped into four subscales. Item scores range from 1 to 5. The PDQL‐Summary Index ranges from 37 to 185, with higher scores reflecting better quality of life (Deboer 1996).
Short Form‐36 or ‐12 － generic short‐form health survey consisting of 36 or 12 questions. The SF‐36 consists of eight scaled scores assessing vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Scores range from 0 to 100, with higher scores corresponding to better quality of life (Ware 1992).

Adverse events (e.g. fractures, pain).

Compliance (e.g. participant adherence, treatment fidelity).

Economic analysis.

Search methods for identification of studies

The review is based on the Movement Disorders Group search strategy and the following more general search strategy:

Physiotherapy OR physical therapy OR exercise OR rehabilitation.
Parkinson OR Parkinson's disease OR Parkinsonism.
#a AND #b.

Further details on this search strategy are available in the Group's module within The Cochrane Library (www.cochrane.org). This includes explanations of the acronyms, sources, and Websites.

We undertook a systematic search of the literature up to the end of January 2012 for publications or abstracts describing relevant trials. This included searching:

General biomedical and science electronic databases (without date limiters) including the Movement Disorders Review Group Specialized Register, The Cochrane Library, MEDLINE (1966‐2012), EMBASE (1974‐2012), CINAHL (1982‐2012), and ISI‐SCI (1981‐2012); rehabilitation databases: AMED (1985‐2012), REHABDATA (1995‐2012), REHADAT, and GEROLIT (1979‐2012); English language databases of foreign language research and third world publications: LILACS (1982‐2012), MedCarib (17th Century‐2012), and IMEMR (1984‐2012).
The Cochrane Controlled Trials Register, the CentreWatch Clinical Trials listing service, the metaRegister of Controlled Trials, ClinicalTrials.gov, RePORT, PEDro, NIDRR, and NRR.
Handsearching of general (Lancet, BMJ, JAMA) and specific journals (Movement Disorders, Neurology, Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Physiotherapy, Physical Therapy) from 2001 to the end of January 2012.
The reference lists of retrieved papers and review articles.
Abstract books and conference proceedings. This included The XIII International Congress on Parkinson's Disease (1999), The International Congress of Parkinson's Disease and Movement Disorders (1990, 92, 94, 96, 98, 2000, 02, 04, 05, 06, 07, 08, 09, 10, 11), World Congress on Parkinson's Disease and Related Disorders (2009, 2012), and The American Academy of Neurology 51st Annual Meeting (1999).
Grey literature databases (including theses): Conference Proceedings Citation Index (1982‐2010), DISSABS (1999‐2012), Conference Papers Index (1982‐2012), Index to Theses (1970‐2012), Electronic Theses Online Service (EThOS) (16th century‐2012), and ProQuest dissertations and theses databases (1861‐2012).

Data collection and analysis

Selection of studies

Abstracts of potentially relevant studies from search results were screened by two of the the four review authors involved in study selection (CT, SP, CH, LS). The full paper was obtained if the abstract did not provide sufficient information for investigators to determine eligibility for inclusion in the review. Disagreement was resolved by referral to an additional review author (RS). We contacted authors of potentially eligible studies for further information if details of the trial were unclear.

Data extraction and management

Four review authors (CT, SP, CM, and CH) independently assessed the identified papers and abstracts for trial details and outcome data, and each eligible study was considered by two of these four authors. This was validated by discussion, with any discrepancies resolved by consensus. We recorded trial details on a standard trial description form and included the following: trial name, trial group, authors, randomised comparison, treatment schedule (including duration, number of sessions, type of intervention), other therapy, eligibility criteria, method of randomisation, allocation concealment, blinding, accrual period, number of participants randomised, number of dropouts, duration of follow‐up, outcomes reported, use of intention‐to‐treat analysis, and publication date(s). Outcome data extracted included data on gait, functional mobility and balance, falls, clinician‐rated disability scale and patient‐rated quality of life, adverse events, compliance/withdrawals, and health economics where available.

We contacted the authors of any eligible unpublished studies to ask whether further details and data for their trial could be provided.

Assessment of risk of bias in included studies

We assessed the full papers for methodological quality by recording eligibility criteria, methods of randomisation and blinding, concealment of allocation, similarity of participants in treatment groups at baseline, cointervention(s) constant, use of active or credible placebo, whether an intention‐to‐treat analysis was performed, and the numbers of participants lost to follow‐up and missing values (see Risk of Bias tables under Characteristics of included studies).

Data synthesis

We combined the results of all trials using standard meta‐analytic methods to estimate an overall effect for physiotherapy intervention versus no physiotherapy intervention.

All outcomes with data available for meta‐analysis were continuous variables, so we calculated the mean difference between treatment arms using mean difference methods (Fleiss 1993). In summary, this involved calculating for each trial the mean change (and standard deviation) from baseline to the postintervention time point for the intervention and no intervention groups. From these, the mean difference and its variance between arms for each trial could be calculated. In some studies, the standard deviation for the mean change was not reported; in these cases, we imputed this standard deviation using the standard deviations for baseline and final scores. To do this, we used the following formula to estimate the variance of the change in score:

var_diff = var_pre + var_post – 2r√(var_pre var_post)

where var_diff is the variance of the change score; var_pre is the variance of the baseline score; var_post is the variance of the final score; and r is the correlation between pretreatment and post‐treatment scores. We assumed a correlation co‐efficient of 0.5, which is a conservative estimate, to reduce the chance of false‐positive results (Higgins 2011).

These values were then combined using weighted mean difference methods to obtain the overall pooled estimate of the mean difference, with 95% confidence interval, for physiotherapy intervention versus no physiotherapy intervention (control).

If any trials with three or more intervention arms were identified, the following assumptions were made for the analysis:

If the trial was comparing two or more physiotherapy interventions within the same classification (see subgroup analysis later) versus no intervention, then we combined the data for these physiotherapy interventions to give one comparison of physiotherapy intervention versus no intervention.
If the trial was comparing two or more physiotherapy interventions in different classifications versus no intervention, then we included that trial in each relevant physiotherapy intervention classification. This meant that some trials were included multiple times in the analysis, and the control arms from these trials were counted more than once in the analysis.

The primary analysis was a comparison of physiotherapy intervention versus no physiotherapy intervention (control) based on change from baseline to the first assessment after the treatment period (which in most cases was immediately post intervention). This was chosen as the primary analysis for this review, as in most trials this was the main data analysis, and few trials reported data at longer‐term assessment points (i.e. after six months). Also, some trials allowed participants in the 'no intervention' arm to receive physiotherapy intervention after this point. So this allowed a clean comparison of physiotherapy intervention versus no physiotherapy intervention.

Subgroup analysis and investigation of heterogeneity

The different trials implemented various types of physiotherapy intervention. Therefore trials were divided according to the type of intervention administered:

General physiotherapy versus control.
Exercise versus control.
Treadmill versus control.
Cueing versus control.
Dance versus control.
Martial arts versus control.

To assess for differences between the different types of interventions involved, we performed indirect comparisons using tests of heterogeneity and I² values to investigate whether the treatment effect differed across the different interventions (Deeks 2001; Higgins 2003). The I² value describes the percentage of variability in effect estimates that is due to heterogeneity rather than to sampling error (chance) (Higgins 2003). These tests may suggest the possible superiority of one type of intervention over another, and may provide clinicians and patients with more reliable information upon which to base decisions about therapy. However, as with all subgroup comparisons, these analyses should be interpreted with caution and should be considered hypothesis generating (Assmann 2000; Clarke 2001).

Results

Description of studies

We identified 76 randomised trials of physiotherapy intervention in PD patients. We excluded 31 studies (see Characteristics of excluded studies). The reasons for excluding these trials were as follows: cross‐over study with data not presented for the first treatment period or cross‐over over a short period (e.g. 1 day) (n=6), not randomised or not properly randomised (n=7), no outcome measures relevant to our review (n=4), multidisciplinary therapy rehabilitation trial (n=4), study was confounded (n=2) and treatment given in trial was not usually used by physiotherapists (n=6), excessive number of withdrawals (n=1), and insufficient information (n=1). There were also six ongoing trials for which data were not yet available (see Characteristics of ongoing studies). Therefore, 39 trials were available for inclusion in the review compared with 11 in the 2001 review (Figure 1).

The number of participants randomly assigned into the 39 trials ranged from six to 153 participants, with 1827 participants randomly assigned in total (giving an average trial size of nearly 50 participants) (Characteristics of included studies). The assessment period ranged from three weeks to 12 months. The mean age of participants in the trials was 67 years, 64% were male, the mean Hoehn & Yahr stage was 2.4, and participants had had PD for approximately six years (Table 6).

1. Key Characteristics of Studies.

Study	Number Randomised	Mean Age (yrs)	Mean Hoehn & Yahr Stage	Duration of Disease (yrs)	% Male	Duration of Treatment	Design	Location	Type of Treatment
Allen 2010	48	67		8	54	48‐72 hrs/24 weeks	Parallel	Outpatient	Exercise
Almeida 2012	42	68.4		5.3	74	9 hrs/6 weeks	Parallel	Outpatient	Cueing
Ashburn 2007	142	72.15	3.13	8.35	61	42 hrs/6 weeks	Parallel	Home	Exercise
Boehm 2011	110	69.4			60	12 weeks	Cross‐over		Exercise
Cakit 2007	54	71.8		5.58	52	30‐min sessions/ 8 weeks	Parallel	Outpatient	Treadmill
Canning 2008	20	61				9‐12 hrs/6 weeks	Parallel	Home	Treadmill
Cerri 1994	6					15 hrs/3 weeks	Parallel	Outpatient/Home	Exercise
Chandler 1999	67	65.5	2.6		60	5 times/52 weeks	Parallel	Home	Physio
de Bruin 2010a	22	65.6	2.2	5.5	50	18 hrs/12 weeks	Parallel	Outpatient	Cueing
de Bruin 2010b	13					3 per week/13 weeks	Parallel	Outpatient	Cueing
Duncan 2012	62	70.3	2.5		56	24 hrs/2 weeks	Parallel		Dance
Ellis 2005	68	64	2.4		75	18 hrs/6 weeks	Cross‐over	Outpatient	Physio
Fisher 2008	30	62.9	1.9	1.1	63	24 sessions/8 weeks	Parallel	Outpatient	Treadmill/Physio
Ganesan 2010	20					8 hrs/4 weeks	Parallel	Outpatient	Treadmill
Goodwin 2009	130	71.1	2.5	8.7	57	10 weeks	Parallel	Outpatient	Exercise
Haase 2011	26	66			52	4 mins/single session	Parallel		Cueing
Hackney 2009	75	66.6	2.1	7.7	74	20 hrs/13 weeks	Parallel	Outpatient	Dance/Martial Arts
Homann 1998	15					14 units/5 weeks	Parallel	Outpatient	Physio
Keus 2007	27	67.95	2.4	6.5	81	1 or 2 per week/10 weeks	Parallel	Outpatient	Physio
Klassen 2007	26	66.2	1.6	4.7	74	15‐30 hrs/12 weeks	Parallel	Outpatient	Exercise
Kurtais 2008	27	64.75	2.1	5	50	12 hrs/6 weeks	Parallel	Outpatient	Treadmill
Lehman 2005	11	75.8		6.5	73	5 per week/2 weeks	Parallel	Outpatient	Cueing
Mak 2008	60	64	2.7	6		4‐6 hrs/4 weeks	Parallel	Outpatient	Cueing/Exercise
Marjama‐Lyons 2002	30					24 hrs/12 weeks	Parallel	Outpatient	Martial Arts
Meek 2010	39	64.2		4.9	79	12 weeks	Parallel	Outpatient	Exercise
Nieuwboer 2007	153	67.1	2.8	7.5	58	4.5 hrs/3 weeks	Cross‐over	Home	Cueing
Protas 2005	18	72.5	2.9	7.6	100	24 hrs/8 weeks	Parallel	Outpatient	Treadmill
Purchas 2007	20	70	2.15		61	12 hrs/12 weeks	Cross‐over		Martial Arts
Sage 2009a	53	66		3.5	54	18‐24 hrs/10‐12 weeks	Parallel	Outpatient	Exercise
Schenkman 1998	51	70.9	2.7		74	22.5‐30 hrs/10 weeks	Parallel	Outpatient	Exercise
Schilling 2008	18	59.2	2		61	2 per week/8 weeks	Parallel	Outpatient	Exercise
Schmitz‐Hubsch 2006	56	63.5		5.8	77	16 hrs/24 weeks	Parallel	Outpatient	Martial Arts
Shankar 2008	28	66	2.4	7.7	50	18 hrs/12 weeks	Parallel	Outpatient	Cueing
Shankar 2009	20					8 hrs/8 weeks	Parallel	Outpatient	Treadmill
Stack 2012	47					12 hrs/4 weeks	Parallel	Home	Physio
Stozek 2003	61	65.5	2.3	4.5	48	56 hrs/4 weeks	Parallel	Outpatient	Exercise
Taheri 2011	24					40 hrs/ 10 weeks	Parallel		Exercise
Talakad 2011	60					8 hrs/4 weeks	Parallel	Outpatient	Physio/treadmill
Thaut 1996	37	71.3	2.5	7.7	70	10.5 hrs/3 weeks	Parallel	Home	Exercise/Cueing

Date	Event	Description
16 April 2013	New citation required but conclusions have not changed	New studies added, conclusions unchanged.
7 September 2012	New search has been performed	Search updated to 31 January 2012. New studies added, conclusions unchanged.
30 August 2011	New search has been performed	Converted to new review format. Updated search till 31 December 2010. New studies, conclusions changed.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 2 or 6 Minute Walk Test (m)	6	242	Mean Difference (IV, Fixed, 95% CI)	13.37 [0.55, 26.20]
1.1 Exercise v Control	3	98	Mean Difference (IV, Fixed, 95% CI)	10.14 [‐5.70, 25.97]
1.2 Treadmill v Control	1	18	Mean Difference (IV, Fixed, 95% CI)	‐4.80 [‐36.63, 27.03]
1.3 Dance v Control	2	100	Mean Difference (IV, Fixed, 95% CI)	38.94 [‐3.18, 81.06]
1.4 Martial Arts v Control	1	26	Mean Difference (IV, Fixed, 95% CI)	43.6 [0.71, 86.49]
2 10 or 20m Walk Test (s)	4	169	Mean Difference (IV, Fixed, 95% CI)	0.40 [0.00, 0.80]
2.1 Exercise v Control	3	145	Mean Difference (IV, Fixed, 95% CI)	0.41 [0.02, 0.81]
2.2 Treadmill v Control	1	24	Mean Difference (IV, Fixed, 95% CI)	‐0.8 [‐4.41, 2.81]
3 Speed (m/s)	15	814	Mean Difference (IV, Fixed, 95% CI)	0.04 [0.02, 0.06]
3.1 General Physiotherapy v Control	3	137	Mean Difference (IV, Fixed, 95% CI)	0.09 [0.01, 0.17]
3.2 Exercise v Control	5	248	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.01, 0.06]
3.3 Treadmill v Control	3	56	Mean Difference (IV, Fixed, 95% CI)	0.04 [‐0.04, 0.12]
3.4 Cueing v Control	6	299	Mean Difference (IV, Fixed, 95% CI)	0.05 [0.02, 0.09]
3.5 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.16, 0.22]
3.6 Martial Arts v Control	1	26	Mean Difference (IV, Fixed, 95% CI)	‐0.09 [‐0.22, 0.04]
4 Cadence (steps/min)	7	350	Mean Difference (IV, Fixed, 95% CI)	‐1.57 [‐3.81, 0.67]
4.1 General Physiotherapy v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	‐2.40 [‐11.12, 6.32]
4.2 Exercise v Control	2	68	Mean Difference (IV, Fixed, 95% CI)	‐1.70 [‐6.30, 2.90]
4.3 Treadmill v Control	2	38	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐6.48, 6.39]
4.4 Cueing v Control	4	224	Mean Difference (IV, Fixed, 95% CI)	‐1.74 [‐4.70, 1.21]
5 Stride Length (m)	6	225	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.02, 0.08]
5.1 General Physiotherapy v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.19, 0.15]
5.2 Exercise v Control	1	22	Mean Difference (IV, Fixed, 95% CI)	0.17 [‐0.03, 0.37]
5.3 Treadmill v Control	2	38	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.07, 0.14]
5.4 Cueing v Control	3	71	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.02, 0.17]
5.5 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.10, 0.24]
5.6 Martial Arts v Control	1	26	Mean Difference (IV, Fixed, 95% CI)	‐0.1 [‐0.23, 0.03]
6 Step Length (m)	5	383	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐0.00, 0.04]
6.1 General Physiotherapy v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.10, 0.06]
6.2 Exercise v Control	2	148	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.02, 0.04]
6.3 Treadmill v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.08, 0.10]
6.4 Cueing v Control	2	195	Mean Difference (IV, Fixed, 95% CI)	0.04 [0.01, 0.07]
7 Freezing of Gait Questionnaire	4	298	Mean Difference (IV, Fixed, 95% CI)	‐1.41 [‐2.63, ‐0.19]
7.1 Exercise v Control	1	45	Mean Difference (IV, Fixed, 95% CI)	‐2.40 [‐5.76, 0.96]
7.2 Cueing v Control	1	153	Mean Difference (IV, Fixed, 95% CI)	‐0.87 [‐2.43, 0.69]
7.3 Dance v Control	2	100	Mean Difference (IV, Fixed, 95% CI)	‐2.21 [‐4.63, 0.22]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Timed Up & Go (s)	9	639	Mean Difference (IV, Fixed, 95% CI)	‐0.63 [‐1.05, ‐0.21]
1.1 Exercise v Control	6	370	Mean Difference (IV, Fixed, 95% CI)	‐0.21 [‐0.88, 0.45]
1.2 Cueing v Control	2	195	Mean Difference (IV, Fixed, 95% CI)	‐0.77 [‐2.05, 0.52]
1.3 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	‐3.10 [‐7.76, 1.56]
1.4 Martial Arts v Control	1	26	Mean Difference (IV, Fixed, 95% CI)	‐0.9 [‐1.50, ‐0.30]
2 Functional Reach (cm)	4	393	Mean Difference (IV, Fixed, 95% CI)	2.16 [0.89, 3.43]
2.1 Exercise v Control	3	240	Mean Difference (IV, Fixed, 95% CI)	2.46 [0.94, 3.97]
2.2 Cueing v Control	1	153	Mean Difference (IV, Fixed, 95% CI)	1.46 [‐0.88, 3.80]
3 Berg Balance Scale	5	385	Mean Difference (IV, Fixed, 95% CI)	3.71 [2.30, 5.11]
3.1 Exercise v Control	3	280	Mean Difference (IV, Fixed, 95% CI)	2.79 [0.50, 5.08]
3.2 Treadmill v Control	1	31	Mean Difference (IV, Fixed, 95% CI)	8.29 [1.07, 15.51]
3.3 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	5.15 [0.42, 9.88]
3.4 Martial Arts v Control	1	26	Mean Difference (IV, Fixed, 95% CI)	3.80 [1.81, 5.79]
4 Activity Specific Balance Confidence	3	66	Mean Difference (IV, Fixed, 95% CI)	2.40 [‐2.78, 7.57]
4.1 Exercise v Control	2	38	Mean Difference (IV, Fixed, 95% CI)	3.63 [‐2.09, 9.36]
4.2 Cueing v Control	1	28	Mean Difference (IV, Fixed, 95% CI)	‐3.1 [‐15.18, 8.98]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Falls Efficacy Scale	4	353	Mean Difference (IV, Fixed, 95% CI)	‐1.91 [‐4.76, 0.94]
1.1 Exercise v Control	2	169	Mean Difference (IV, Fixed, 95% CI)	‐2.35 [‐5.38, 0.69]
1.2 Treadmill v Control	1	31	Mean Difference (IV, Fixed, 95% CI)	‐14.67 [‐39.11, 9.77]
1.3 Cueing v Control	1	153	Mean Difference (IV, Fixed, 95% CI)	3.32 [‐5.38, 12.02]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 UPDRS ‐ Total	3	207	Mean Difference (IV, Fixed, 95% CI)	‐6.15 [‐8.57, ‐3.73]
1.1 General Physiotherapy v Control	2	85	Mean Difference (IV, Fixed, 95% CI)	‐4.84 [‐7.63, ‐2.04]
1.2 Exercise v Control	1	102	Mean Difference (IV, Fixed, 95% CI)	‐12.90 [‐18.30, ‐7.50]
1.3 Treadmill v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	1.1 [‐9.60, 11.80]
2 UPDRS ‐ Mental	2	105	Mean Difference (IV, Fixed, 95% CI)	‐0.44 [‐0.98, 0.09]
2.1 General Physiotherapy v Control	2	85	Mean Difference (IV, Fixed, 95% CI)	‐0.47 [‐1.05, 0.11]
2.2 Treadmill v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	‐0.3 [‐1.64, 1.04]
3 UPDRS ‐ ADL	3	157	Mean Difference (IV, Fixed, 95% CI)	‐1.36 [‐2.41, ‐0.30]
3.1 General Physiotherapy v Control	2	85	Mean Difference (IV, Fixed, 95% CI)	‐1.62 [‐2.77, ‐0.47]
3.2 Treadmill v Control	1	20	Mean Difference (IV, Fixed, 95% CI)	1.50 [‐1.81, 4.81]
3.3 Dance v Control	1	52	Mean Difference (IV, Fixed, 95% CI)	‐2.50 [‐6.83, 1.83]
4 UPDRS ‐ Motor	12	593	Mean Difference (IV, Fixed, 95% CI)	‐5.01 [‐6.30, ‐3.72]
4.1 General Physiotherapy v Control	3	137	Mean Difference (IV, Fixed, 95% CI)	‐3.08 [‐5.24, ‐0.92]
4.2 Exercise v Control	2	148	Mean Difference (IV, Fixed, 95% CI)	‐10.02 [‐12.81, ‐7.23]
4.3 Treadmill v Control	2	38	Mean Difference (IV, Fixed, 95% CI)	0.05 [‐3.93, 4.03]
4.4 Cueing v Control	3	92	Mean Difference (IV, Fixed, 95% CI)	‐3.15 [‐6.68, 0.37]
4.5 Dance v Control	2	100	Mean Difference (IV, Fixed, 95% CI)	‐8.48 [‐12.76, ‐4.19]
4.6 Martial Arts v Control	2	78	Mean Difference (IV, Fixed, 95% CI)	‐5.82 [‐9.79, ‐1.85]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PDQ‐39 Summary Index	7	405	Mean Difference (IV, Fixed, 95% CI)	‐0.38 [‐2.58, 1.81]
1.1 General Physiotherapy v Control	1	52	Mean Difference (IV, Fixed, 95% CI)	0.68 [‐6.84, 8.20]
1.2 Exercise v Control	3	104	Mean Difference (IV, Fixed, 95% CI)	0.32 [‐3.83, 4.48]
1.3 Treadmill v Control	1	18	Mean Difference (IV, Fixed, 95% CI)	‐0.7 [‐7.69, 6.29]
1.4 Cueing v Control	1	153	Mean Difference (IV, Fixed, 95% CI)	‐1.58 [‐5.45, 2.29]
1.5 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	‐2.34 [‐8.83, 4.15]
1.6 Martial Arts v Control	1	30	Mean Difference (IV, Fixed, 95% CI)	3.05 [‐3.81, 9.91]
2 PDQ‐39 Mobility	2	105	Mean Difference (IV, Fixed, 95% CI)	‐1.43 [‐8.03, 5.18]
2.1 General Physiotherapy v Control	1	27	Mean Difference (IV, Fixed, 95% CI)	6.23 [‐3.85, 16.31]
2.2 Dance v Control	1	48	Mean Difference (IV, Fixed, 95% CI)	‐10.41 [‐22.50, 1.68]
2.3 Martial Arts v Control	1	30	Mean Difference (IV, Fixed, 95% CI)	‐3.65 [‐16.30, 9.00]

Methods	Parallel group design. Randomised using a randomisation schedule with randomly permuted block sizes, developed by an investigator not involved in subject recruitment or assessment. Data analysed on an intention‐to‐treat basis. Treated as outpatients and at home for 48‐72 hours over 6 months. Assessed at baseline and post intervention. Assessors were blinded.
Participants	24 participants in the exercise group and 24 in the control group. 3 drop‐outs in the exercise group. Participants' mean age was 66 years (exercise) and 68 years (control); male/female 13/11 (exercise) and 13/11 (control); duration of PD 7 years (exercise) and 9 years (control). Hoehn and Yahr stage not reported. Inclusion criteria: diagnosis of idiopathic Parkinson's disease, able to walk independently (with or without an aid), fallen in the last year or deemed to be at risk of falling, 30‐80 years of age, and on the same PD medication for the past 2 weeks. Exclusion criteria: significant cognitive impairment (Mini Mental State Examination [MMSE] <24), had another neurological/musculoskeletal/cardiopulmonary/metabolic condition that would interfere with safe conduct of the training or testing protocol.
Interventions	Exercise: 40‐ to 60‐minute program of progressive lower limb strengthening and balance exercises (targeted leg muscle strength, balance, and freezing). Once‐monthly exercise classes, with the remaining exercise sessions at home. Control: usual care with advice on fall prevention and falls diary recording any fall. Drug therapy was allowed to vary.
Outcomes	PD falls risk score. Knee extensor strength. Coordinated stability. Sway. Maximum balance range in standing. Alternate step test. Freezing of Gait Questionnaire. Sit‐to‐stand time. Fast walking speed. Comfortable walking speed. Short physical performance battery. Falls Efficacy Scale － International. PDQ‐39. Participants were assessed in their home about 1 hour after taking their usual PD medication, and the order of measurements was standardised.
Notes	Participants in the exercise group who experienced freezing of gait were also instructed in cueing strategies to reduce freezing as part of their exercise program. Exercise group completed a mean of 70% of total prescribed exercise sessions.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Randomly permuted block size.
Concealment of Allocation	Unclear risk	No information provided.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	6% overall, but all from exercise group.
Intention To Treat Analysis	Low risk	An intention‐to‐treat approach was used for all analyses.
Cointerventions Constant	Unclear risk	Allowed variation in levodopa therapy.
Credible Placebo	Low risk	Falls prevention advice given in both arms.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Parallel group design. Randomised by pulling allocation out of a hat. Analysed on a per protocol basis. Treated as outpatients for 9 hours over 6 weeks. Assessed at baseline, 6 weeks, and 12 weeks. Assessors were blinded for UPDRS III evaluation.
Participants	14 participants in the Overground walking group (OG), 14 in the Treadmill walking group (TM), and 14 in the control group (CL). 2 dropouts in TM group, 1 dropout in CL group. Participants' mean age 73.9 years (OG), 63.9 years (TM), and 67.4 years (CL); male/female 12/2 (OG), 8/6 (TM), and 11/3 (CL); Hoehn and Yahr stage not stated; duration of PD not stated. Inclusion criteria: confirmed as having clinically typical Parkinson's disease by at least one movement disorders neurologist. Exclusion criteria: past history of neurological conditions other than Parkinson's disease, orthopaedic or visual disturbances that severely impaired walking ability, unable to independently walk down an 8‐meter GAITRite carpet for a total of 10 trials.
Interventions	OG: walk down equally spaced transverse lines presented on a 16‐m carpet. The cues were white lines of tape. Participants asked to walk across the lines, turn, and continue back. Spacings were set at 8% greater than the initial step length of any of the groups (70 cm). 30‐Minute session with mandatory 2‐minute break every 8 minutes, additional rest allowed if necessary, but a total of 24 minutes of walking was required for a gait session to be considered complete. TM: Walk on a treadmill presented with equally distributed standardised transverse white lines. Spacings were set at 8% greater than the initial step length of any of the groups (70 cm). 30‐minute session with mandatory 2‐minute break every 8 minutes, additional rest allowed if necessary, but a total of 24 minutes of walking was required for this gait session to be considered complete. CL: instructed to continue their usual activities. Participants were optimally medicated at time of all training and testing sessions and remained on stable regimen throughout trial period.
Outcomes	Step length. UPDRS III. Timed up and go. Gait speed. Cadence. Double support time. Step time. Step‐to‐step variability, Step time variability. 30‐Ssecond chair stand.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria stated.
Randomisation Method	High risk	Allocation pulled out of hat.
Concealment of Allocation	High risk	Allocation pulled out of hat.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	Withdrawals at less than 10%.
Intention To Treat Analysis	High risk	Analysed on a per protocol basis.
Cointerventions Constant	Low risk	Participants maintained stable drug regiment throughout trial period.
Blinded Assessors	Low risk	Assessors blind for UPDRS III evaluation only. (This is the only subjective outcome.)

Methods	Parallel group design. Stratified by NHS using blocks of size four. Random allocation by telephoning the medical statistics group at University of Southampton. Participants were informed of their allocation by telephone. Data analysed on an intention‐to‐treat basis. Treated as outpatients 7 times a week for a 6‐week period, for a total period of 42 hours. Assessed at baseline, 8 weeks, and 6 months.
Participants	70 participants in the exercise group and 72 in the control group. 6 dropouts in the exercise group and 8 in the control group. Participants' mean age 72.7 years (exercise), 71.6 years (control); male/female 38/32 (exercise), 48/24 (control); Hoehn and Yahr stage 3.14 (exercise), 3.11 (control); duration of PD 7.7 years (exercise), 9 years (control). Inclusion criteria: confirmed diagnosis of Parkinson's disease, independently mobile, living at home in the community, experienced more than one fall in the previous 12 months, passed a screening for gross cognitive impairment (Mini‐Mental State). Exclusion criteria: unable to participate in assessments because of pain, acute medical condition, in receipt of or soon to receive treatment.
Interventions	Exercise: personalised home‐based exercise and strategy programme. After assessment, treatment goals were established with participants, and exercises from the exercise menu were taught. Participants were visited weekly at home by a physiotherapist for approximately 1 hour. 6 levels of exercise progression comprised muscle strengthening, range of movement, balance training, and walking. Strategies of falls prevention and movement initiation and compensation taught by physiotherapist. Participants were asked to complete the exercises daily for max of 1 hour and to keep a record. Phoned monthly to encourage exercises. Control: usual care, contact with local Parkinson's disease nurse. Drug therapy was not described.
Outcomes	Self‐reported falls diary. Functional reach. Timed up and go test. Chair stand test. Berg balance test. Euroqol‐5d, QoL thermometer. Self‐assessment Parkinson's disease disability scale. Tests were carried out midway between drug doses.
Notes	At 6 months, 34% in the control group were participating in extra rehabilitation compared with 25% in the exercise group.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Block randomisation (block size 4).
Concealment of Allocation	Low risk	Telephone call to central office.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	6% at 8 weeks and 8% at 6 months.
Intention To Treat Analysis	Low risk	Analysis was on an intention‐to‐treat basis.
Cointerventions Constant	Unclear risk	Drug therapy was not described.
Credible Placebo	Low risk	Controls had contact with Parkinson's disease nurse.
Blinded Assessors	Unclear risk	Assessor remained blind to group allocation but reported being aware of the allocation of 18 exercise and 11 control participants at 8 weeks, and 25 exercise and 14 control participants at 6 months.

Methods	Cross‐over design. Random allocation generated and implemented by trial coordinator. Analysed on a per protocol basis. Treated for 12 weeks. Assessed at baseline, 12 weeks, and 24 weeks. Assessors were blinded for UPDRS III evaluation.
Participants	55 participants in sensory attention focused exercise group (SAFE) and 55 in control group . 5 dropouts in SAFE group, 3 dropouts in control group. Participants' mean age 67.4 years (SAFE), 65.8 years (control); male/female 28/22 (SAFE), 30/22 (control); Hoehn and Yahr stage not stated; duration of PD 5.4 years (SAFE), 5.2 years (control). Inclusion criteria: idiopathic Parkinson's disease diagnosed by neurologist or movement disorders specialist according to international clinical diagnosis criteria, able to commit to study guidelines for 24 weeks. Exclusion criteria: score lower than 76 on 3MS (extended MMSE).
Interventions	Sensory attention focused exercise. Control: no intervention. Drug therapy was not described.
Outcomes	UPDRS I, II, & III. Timed up and go. Step length. Step length variability. Gait speed. Grooved peg‐board. 30 second chair stand.
Notes	Abstract and unpublished data. Baseline characteristics do not include dropouts.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria stated.
Randomisation Method	Unclear risk	Randomisation method not clear.
Concealment of Allocation	Unclear risk	Randomisation method not clear.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	Withdrawals at 7%.
Intention To Treat Analysis	Low risk	Analysed on a per protocol basis.
Cointerventions Constant	Low risk	Drug therapy constant.
Blinded Assessors	Low risk	Assessors were blinded for UPDRS III evaluation.

Methods	Parallel group design. Method of randomisation not stated. Method of analysis not described. Treated as outpatients for an unspecified time over 8 weeks (30‐minute sessions). Assessed at baseline and immediately after treatment. Assessors were blinded.
Participants	27 participants in the treadmill group and 27 in the control group. 6 dropouts in the treadmill group, 17 dropouts in the control group. No baseline characteristics given for dropouts. Participants' mean age 71.8 years; male/female 16/15. The Hoehn and Yahr scores were not given. The mean duration of PD was 5.6 years. Inclusion criteria: Parkinson's disease patients who fulfilled the UK Parkinson's Disease Society Brain Bank Criteria, were medically stable, were able to walk 10‐metre distance at least 3 times with or without assistive device, able to provide informed consent. Exclusion criteria: participants who had neurological conditions other than idiopathic Parkinson's disease, scored greater than 3 in Hoehn and Yahr, scored less than 20 in MMSE, postural hypotension, cardiovascular disorders, class C or D exercise risk by the American College of Sports Medicine (ACSM) criteria, musculoskeletal disorders, visual disturbance or vestibular dysfunction limiting locomotion or balance.
Interventions	Treadmill: 8‐Week exercise program using incremental speed‐dependent treadmill training. Programme comprised stretching, range of motion exercise, and treadmill training. The treadmill session lasted for 30 minutes and participants were observed during treadmill training by a physiatrist, who gave no assistance in the actual performance of the movements. Maximum tolerated walking speed was determined before the training session began. This speed then was halved and was used for a 5‐minute warm‐up period. After the warm‐up period, the belt speed was increased by increments of 0.6 km/h every 5 minutes. When the belt speed was increased to the highest speed at which the participant could walk safely and without stumbling, this maximum‐achieved belt speed was maintained for 5 minutes and then was followed by 0.6‐km/h decrements. The participant maintained the rest of the treadmill session at this speed for 15 minutes. Control: no intervention. Drug therapy was constant during the trial.
Outcomes	Berg Balance Test. Dynamic Gait Index. Falls Efficacy Scale. Walking distance on treadmill. Tolerated maximum speed on treadmill (km/h). Examinations took place when participants were in the 'on' phase of medication.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Unclear risk	Method of randomisation not stated.
Concealment of Allocation	Unclear risk	Method of randomisation not stated.
Similarity at Baseline	Unclear risk	Baseline data given overall, not split by treatment group.
Withdrawals Described	High risk	43% withdrawals.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Low risk	Drug therapy was constant during the trial.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Parallel group design. Randomisation method was not stated. Method of analysis not described. Treated as outpatients for 15 hours over 3 weeks followed by a home exercise program for 2 months, then the cycle was repeated. (Total of 30 hours therapy.) Assessed at baseline and immediately after treatment. Not stated whether assessors were blinded.
Participants	3 participants in the exercise group and 3 in the control group. Dropouts not described. Participants' were all aged between 58 and 68 years at Hoehn and Yahr stage 3 and 4. No data given for the sex of the participants. Inclusion criteria: Parkinson's disease, stage 3 and 4 of Hoehn and Yahr scale, treated with L‐dopa for longer than 4 years with incomplete control of rigidity and tremor. No exclusion criteria stated.
Interventions	Exercise: Individual. Physical exercise program with neuromuscular facilitation techniques to improve posture, inhibit rigidity, and 'conscientize' movements. Control: Untreated. Drug therapy was allowed to vary during trial.
Outcomes	Webster Disability Scale. Activity of daily living. L‐dopa reduction. Not stated when examinations took place.
Notes	Abstract only. No means and SDs available.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Unclear risk	Randomisation method was not stated.
Concealment of Allocation	Unclear risk	Randomisation method was not stated.
Similarity at Baseline	Unclear risk	Only information given was that all participants were aged between 58 and 68 years and had Hoehn and Yahr stage 3 and 4.
Withdrawals Described	Unclear risk	Dropouts not described.
Cointerventions Constant	Unclear risk	2 participants in the intervention group reduced dose of L‐dopa to avoid side effects. Allowed variation in medication.
Blinded Assessors	Unclear risk	Not stated whether assessors were blinded.

Methods	Parallel group design. Online random number generator used to perform group allocations. Data analysed on an intention‐to‐treat basis. Treated as outpatients for 104 hours over 12 months. Assessed at baseline, 3 months, 6 months, and 12 months. Assessor was blinded.
Participants	32 participants in the dance group and 30 participants in the control group were analysed. 6 dropouts in dance group, 4 in control group. Participants mean age 70.6 years (dance), 69.2 (control). Mean Hoehn and Yahr stage 2.6 (dance), 2.5 (control). Male/female ratio 19/13 (dance), 16/14 (control). Duration of condition 5.4 years (dance), 6.9 (control). Inclusion criteria: Clinically defined 'definite PD.' Exclusion criteria: serious medical condition, evidence of abnormality other than PD‐related changes on brain imaging (previously done for clinical evaluations), history or evidence of musculoskeletal problem.
Interventions	Dance: tango class for 1 hour, twice weekly. Participants danced both leader and follower roles, changed partners frequently, and learned new steps and/or integrated previously learned steps in new ways at each class throughout the 12 months. Control: prescribed no exercise and told to go about living as usual.
Outcomes	MDS‐UPDRS‐III (primary). MDS‐UPDRS‐II & I. MiniBESTest balance test. Freezing of gait questionnaire. 6‐minute walk test Gait speed. Nine‐hole peg test. Participants were assessed while off medication (12‐hour withdrawal).
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria stated.
Randomisation Method	Low risk	Online random number generator.
Concealment of Allocation	High risk	Assigned by principal investigator using online random number generator.
Similarity at Baseline	Low risk	Baseline characteristics similar between groups.
Withdrawals Described	High risk	16% withdrawals.
Intention To Treat Analysis	Unclear risk	Last observation carried forward.
Cointerventions Constant	Low risk	12‐hour withdrawal before assessment.
Blinded Assessors	Low risk	Assessor was blind to group allocation.

Methods	Cross‐over design. Block randomisation procedure was used in which each sealed envelope contained four Group A assignments and four Group B assignments. This process continued until a total of 68 subjects were randomly allocated. Method of analysis not described. Treated as outpatients 2 times a week for 6 weeks for a total of 18 hours (1.5‐hour sessions). Assessed at baseline, immediately after 1st treatment. Immediately before 2nd treatment and 3 months after 2nd treatment. Assessors were blinded.
Participants	35 participants in the physiotherapy group and 33 in the control group. 11 dropouts. Participants' mean age 64 years (physiotherapy), 63 years (control); male/female ratio, 25/10 (physiotherapy), 26/7 (placebo); mean Hoehn & Yahr 2.5 (physiotherapy), 2.4 (control). Inclusion criteria: stable medication usage, Hoehn & Yahr stage 2 or 3, at least 1 score of 2 or more for at least 1 limb for the tremor, rigidity, or bradykinesia item of the UPDRS, ability to walk independently, age 35 to 75 years, no severe cognitive impairment (MMSE ≥24), no other severe neurologic, cardiopulmonary, or orthopaedic disorders, not having participated in a physical therapy or rehabilitation program in the previous 2 months. No exclusion criteria stated.
Interventions	Physiotherapy: 1.5‐hour‐long physical therapy session consisting of stretching, functional training, gait training, auditory cueing, balance, recreational, and relaxation. Control: medical therapy only. It was not stated whether drug therapy was kept constant during the trial.
Outcomes	Sickness Impact Profile (SIP‐68). UPDRS (Sections I, II, III). Comfortable walking speed. Assessments were performed at the same time of day and in the same order. Assessments were performed in the 'on' state for subjects who experience motor fluctuations.
Notes	Of the 68 subjects, 50 attended all treatment sessions.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Blocked randomisation (block size 8) with sealed envelopes.
Concealment of Allocation	High risk	Sealed envelopes, which contained 8 group allocations (4 per group).
Similarity at Baseline	Low risk
Withdrawals Described	High risk	16% at the end of the trial.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Unclear risk	It was not stated whether drug therapy was kept constant during the trial.
Blinded Assessors	Low risk	Assessors were blind to group allocation.

Methods	Parallel group design. Randomisation was done by the subjects with their eyes closed; they selected a card corresponding to one of the three groups. Method of analysis not described. Treated as outpatients for 24 sessions over 8 weeks for both treatment arms, 6 sessions over 8 weeks for control group. Assessed at baseline and immediately post treatment. Assessors were blinded.
Participants	10 participants in the treadmill group, 10 participants in the physiotherapy group and 10 participants in the control arm. No dropouts described. Participants' mean age, 64.1 years (treadmill), 61.5 years (physiotherapy), 63.1 years (control). Male/female ratio, 6/4 (treadmill), 5/5 (physiotherapy), 8/2 (control). Mean Hoehn and Yahr 1.9 in all 3 groups. Mean duration of PD 1.2 years (treadmill), 0.7 years (physiotherapy), 1.5 years (control). Inclusion criteria: early‐stage Parkinson's disease, diagnosis of Parkinson's disease within 3 years of study participation, Hoehn and Yahr stage 1 or 2, 18 years or older, medical clearance from primary care physician to participate in exercise programme, ability to walk. Exclusion criteria: medical or physical screening examination showed a score of less than 24 on the MMSE, revealed physician‐determined major medical problems such as cardiac dysfunction that would interfere with participation; subjects had musculoskeletal impairments or excessive pain in any joint that could limit participation in an exercise programme, had insufficient endurance and stamina to participate in exercise 3 times per week for a 1‐hour session.
Interventions	Treadmill: Level of intensity was defined by MET. High‐intensity exercise greater than 3 METs. Body weight supported (BWS) treadmill training. Goal of each session was to reach and maintain a MET > 3. Exercise progressed by decreasing BWS (initially 10% of subject's body weight) and physical assistance, increasing the treadmill speed and time on the treadmill, with the end goal for each subject to walk on the treadmill continuously for 45 minutes within the MET range. Physiotherapy: less than 3 METs. This group was representative of general or traditional physical therapy. Each 45‐minute session was individualised and consisted of activities from 6 categories: (1) passive range of motion and stretching, (2) active range of motion, (3) balance activities, (4) gait, (5) resistance training, (6) practice of functional activities and transitional movements. Control: zero intensity group. Six 1‐hour education classes taken over an 8‐week period. Drug therapy was constant during the trial.
Outcomes	UPDRS (Total, I, II, and III subscores). Hoehn and Yahr. Functional assessments. Walking test. Sit‐to‐stand test. Transcranial magnetic stimulation. All subjects took their customary medications at the same time relative to each assessment.
Notes	Subjects were allowed to continue their customary exercise routines and filled out a daily exercise diary.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	High risk	Subjects self‐selected a card with eyes closed.
Concealment of Allocation	High risk	Subjects self‐selected a card with eyes closed.
Similarity at Baseline	Low risk
Withdrawals Described	Unclear risk	No dropouts described.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Low risk	All medication kept stable during course of study.
Credible Placebo	Low risk	Education classes attended by controls.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Parallel group design. Telephone randomisation external to the research team with 1:1 allocation in geographical cohorts. Data were analysed on an intention‐to‐treat basis. Treated as outpatients for 10 hours over 10 weeks, then home exercise for 10 weeks. Assessed at baseline and at 20 and 30 weeks. Assessors were not blinded.
Participants	64 participants in the exercise group and 66 in the control group. 7 dropouts in total. Participants' mean age 72.0 years (exercise), 70.1 years (control). Male female ratio, 39/25 (exercise), 35/31 (control). Mean Hoehn and Yahr 2.6 (exercise), 2.4 (control). Mean duration of PD 9.1 years (exercise), 8.2 years (control). Inclusion criteria: diagnosis of idiopathic Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Criteria, self‐reported history of two or more falls in the past year, able to mobilise independently with/without a walking aid, resident in Devon, willingness to be randomly assigned and provide written informed consent. Exclusion criteria: needed supervision or assistance from another person to mobilise indoors, significant comorbidity that affects ability or safety to exercise (e.g. unstable angina, unstable diabetes, significant postural hypotension, severe pain, significant dyskinesia), unable to follow verbal or written instructions in English.
Interventions	Exercise: 10 weeks of supervised group strength and balance training plus 10 weeks of unsupervised home exercises. Control: usual care. Drug therapy could vary.
Outcomes	Falls Incidence. Number of fallers/recurrent faller. Fall‐related injuries. Berg Balance Scale. Timed Up and Go. Fall Efficacy Scale － International. EQ‐5D. Household and recreational physical activity (Phone‐FITT). Not stated when examinations took place.
Notes	Additional information and data obtained from author.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria stated.
Randomisation Method	Low risk	Telephone randomisation external to the research team with 1:1 allocation in geographical cohorts.
Concealment of Allocation	Low risk	Telephone randomisation external to the research team with 1:1 allocation in geographical cohorts.
Similarity at Baseline	Low risk	Characteristics of two groups similar.
Withdrawals Described	Low risk	5% withdrawals.
Intention To Treat Analysis	Low risk	Data were analysed on an intention‐to‐treat basis.
Cointerventions Constant	Unclear risk	Participants changed their medication as appropriate as part of usual care.
Credible Placebo	Unclear risk	Control group received usual care.
Blinded Assessors	High risk	Assessors were not blinded.

Methods	Parallel group design. Block randomisation method used. Analysed on a per protocol basis Treated for a single session including 3 minutes of treatment. Assessment intervals not stated. Assessors not blinded.
Participants	8 participants in the Finger tapping (FT) group, 12 in the Arm swinging group (AS) group, 6 in the control group. 1 dropout from the FT group and 2 from the AS group. Participants' mean age, 67 years (FT), 65 years (AS), 65 years (control); male/female 5/2 (FT), 5/5 (AS), 2/4 (control). Mean Hoehn and Yahr and mean duration of PD not stated. No baseline characteristics were given for dropouts. Inclusion criteria: able to walk independently without assistive devices for at least 14 m at a time no more than 4 times, Hoehn & Yahr stage 0 to 2. Exclusion criteria: severe perceptual deficits, medical complications.
Interventions	Rhythmic finger tapping exercise: participants instructed to tap on a metal plate (while seated) to the beat of an external auditory cue from a metronome set to 120% pretest walking cadence, for three, 1‐minute intervals with 30 seconds of rest between intervals. Rhythmic arm swing exercise: participants instructed to swing their arms (while seated) to the beat from a metronome set to 120% pretest walking cadence, for three, 1‐minute intervals with 30 seconds of rest between intervals. Control: participants were instructed to remain seated for 4 minutes. Drug therapy not described.
Outcomes	9‐Hole peg test. UPDRS III & IV. Berg Balance Scale. Speed. Stride length. Cadence.
Notes	Abstract only.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria stated.
Randomisation Method	Unclear risk	Method of generating blocks not stated.
Concealment of Allocation	Unclear risk	Method of randomisation not clear.
Similarity at Baseline	Unclear risk	Full baseline characteristics not stated.
Withdrawals Described	High risk	Dropouts 12%.
Intention To Treat Analysis	High risk	Per protocol analysis.
Cointerventions Constant	Unclear risk	Drug therapy not described.
Credible Placebo	Low risk	Control group received same time and attention as intervention groups.
Blinded Assessors	High risk	Assessors were not blinded.

Methods	Parallel group design. Participant's names were put into alphabetical order and then randomised using computer‐generated random number tables. Method of analysis not described. Treated as outpatients for 14 'units' over 5 weeks. Assessed at baseline and immediately after treatment. Not stated whether assessors were blinded.
Participants	8 participants in physiotherapy group and 7 in placebo group. No dropouts were described. No baseline characteristics available from abstract. Inclusion criteria: idiopathic Parkinson's disease according to UK Brain Bank diagnostic criteria. No exclusion criteria.
Interventions	Physiotherapy: individual Bobath program focusing on proprioceptive skills to improve posture and gait. Control: untreated. Drugs were stable for duration of therapy.
Outcomes	UPDRS. Axial symptoms. Stride length. Walk speed. Stride cadence.
Notes	Abstract and poster only. No numerical data available.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Participant's names were put into alphabetical order and then they were randomly assigned using computer‐generated random number tables.
Concealment of Allocation	Low risk	Based on information above, assumed treatment allocation performed once all patients recruited.
Similarity at Baseline	Unclear risk	No baseline characteristics available from abstract.
Withdrawals Described	Unclear risk	No dropouts described.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Low risk	Drugs were stable for duration of therapy.
Blinded Assessors	Unclear risk	Not stated whether assessors were blinded.

Methods	Parallel group design. Randomised in blocks of four in order of enrolment. Independently assigned with concealed allocation. The data was analysed on an intention‐to‐treat analysis. Treated as outpatients for an unspecified time, once or twice weekly for 10 weeks. Assessed at baseline and immediately after treatment. Assessor was blinded.
Participants	14 participants in the physiotherapy group and 13 in the control group. 1 dropout from the control group. Participants' median age, 65 years (physiotherapy), 71 years (control). Male:female ratio, 11/3 (physiotherapy), 11/2 (control). Mean Hoehn and Yahr 2.4 in both groups. Mean duration of PD 7 years (physiotherapy), 6 years (control). Inclusion criteria: idiopathic Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Criteria, stable reaction to anti‐Parkinsonian medication, at least one mobility‐related activity limitation within core areas of physiotherapy practice in Parkinson's disease (gait, balance, posture, and transfers) experienced by the participant as important. Exclusion criteria: Hoehn and Yahr stage 5 during the 'on' period, physiotherapy within 4 months before randomisation, severe comorbidity influencing mobility or life threatening (e.g. cancer), not motivated to participate in physiotherapy, severe cognitive impairment defined by an MMSE score ≤ 24, presence of psychiatric impairments.
Interventions	Physiotherapy: Once‐ or twice‐weekly individual physiotherapy sessions. Delivered by a physiotherapist trained in the use of evidence‐based practice guidelines. Interventions included Parkinson's disease－specific techniques such as cueing, cognitive movement strategies, and general techniques such as training of balance, leg strength, and physical fitness. The intervention targeted balance, transfers, posture, and gait, dependent on the participant's main complaint. Control: no physiotherapy. It was not stated whether drug therapy was kept constant during the trial.
Outcomes	Patient preference outcome scale. The Parkinson Activity Scale. Mobility domain of the Dutch validated version of the Parkinson's disease questionnaire. Assessments took place during the participants' subjectively best 'on' phase.
Notes	Most participants received six to thirteen sessions of physiotherapy in the nine‐week period.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Block size of 4.
Concealment of Allocation	Unclear risk	Independently assigned with concealed allocation.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	1 dropout from control group (4%).
Intention To Treat Analysis	Low risk	Data were analysed according to intention‐to‐treat principles.
Cointerventions Constant	Unclear risk	It was not stated whether drug therapy was kept constant during the trial.
Blinded Assessors	Low risk	Assessor was blind to group allocation.

Methods	Parallel group design. Participants randomly allocated to groups by drawing lots. Method of analysis not described. Treated as outpatients for 4 hours (audio‐visual), 6 hours (exercise) over 4 weeks. Assessed at baseline, at 2 weeks, immediately after, and 2 weeks after treatment had ended. Assessor was blinded.
Participants	21 participants in the cueing group, 21 participants in the exercise group, and 18 in the control group. 2 dropouts from the cueing group, 2 from the exercise group, and 4 from the control group. No baseline characteristics given for dropouts. Participants' mean age 63 (cueing), 66 (exercise), 63 (control). No data given for the sex of participants. Hoehn and Yahr stage 2.8 (cueing), 2.7 (exercise), and 2.7 (control). Duration of PD 5.9 years (cueing), 6.1 years (exercise), 5.9 years (control). Inclusion criteria: diagnosed with Parkinson's disease according to Quinn, stable on anti‐Parkinson's disease medications without dyskinesia, orthopaedic, arthritic, or heart problems, aged between 50 and 75 years, perform sit‐to‐stand independently, can follow instructions. No exclusion criteria stated.
Interventions	Cueing: audiovisual cued task‐specific training for 20 minutes three times per week. Received cued sit‐to‐stand training using Equitest‐Balance Master. Visual cue was given on a computer screen with verbal command as auditory cue. Each task lasted 2 minutes, repeated once with 30‐second rests in between. Exercise: 45 minutes of conventional exercise twice a week. Conventional mobility and strengthening exercises for flexors and extensors of trunk, hips, knees, and ankles, followed by sit‐to‐stand practice. Control: no treatment. Drugs stable during therapy.
Outcomes	Peak horizontal speed (used in meta‐analysis). Peak vertical speed. Movement time. 3D kinematics data of sit‐to‐stand. Not stated when during the day tests took place.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	High risk	Drawing lots.
Concealment of Allocation	High risk	Drawing lots.
Similarity at Baseline	Low risk
Withdrawals Described	High risk	13% withdrawals.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Low risk	Drugs stable during therapy.
Blinded Assessors	Low risk	Assessor was blinded to group allocation.

PERMALINK

Physiotherapy versus placebo or no intervention in Parkinson's disease

Claire L Tomlinson

Smitaa Patel

Charmaine Meek

Clare P Herd

Carl E Clarke

Rebecca Stowe

Laila Shah

Catherine M Sackley

Katherine HO Deane

Keith Wheatley

Natalie Ives

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Background

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Search methods for identification of studies

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Data synthesis

Subgroup analysis and investigation of heterogeneity

Results

Description of studies

1.

1. Key Characteristics of Studies.

Risk of bias in included studies

2.

3.

Effects of interventions

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

Discussion

Summary of main results

Quality of the evidence

Authors' conclusions

Implications for practice.

Implications for research.

What's new

History

Acknowledgements

Data and analyses

Comparison 1. Gait Outcomes.

1.1. Analysis.

1.2. Analysis.

1.3. Analysis.

1.4. Analysis.

1.5. Analysis.

1.6. Analysis.

1.7. Analysis.

Comparison 2. Functional Mobility and Balance Outcomes.

2.1. Analysis.

2.2. Analysis.

2.3. Analysis.

2.4. Analysis.

Comparison 3. Falls.

3.1. Analysis.

Methods	Parallel group design. Participants were randomly assigned using computer‐generated random block sizes of four. The data were analysed on an intention‐to‐treat basis. Treated as outpatients for 12 sessions over 12 weeks. Assessed at baseline and immediately after treatment, and at 6 months. Assessor was blinded.
Participants	20 participants in the exercise group and 19 in the control group. 1 dropout in the control group. Participants mean age, 63.4 years (exercise), 64.9 years (control); male/female ratio 15/5 (exercise), 16/3 (control); mean duration of PD 5.1 years (exercise), 4.7 (control). Mean Hoehn and Yahr was not reported. Inclusion criteria: diagnosis of idiopathic Parkinson's disease, aged 18 years or over, no cognitive, sensory, or psychological impairments that may prevent engagement in participation in the study or that put the participant at risk (judged by the referring clinician), able to participate in the study for its full duration, able to walk 10 m using any aid or assistance required. Exclusion criteria: participants unable to meet inclusion criteria, or those unwilling to participate, participants with additional impairments resulting in restriction of mobility, or any contraindications to exercise.
Interventions	Exercise: collaborated with fitness instructors to design a 3‐month individualised, progressive exercise program. Control: received usual care. Drug therapy was allowed to change during the study.
Outcomes	Physical Activity Scale for the Elderly. Accelerometer monitored physical activity. 10‐m walk test. 2‐minute walk test. Lower limb muscle strength and grip strength. Fatigue severity scale. PDQ‐39. Falls. No constraints on timing of assessments.
Notes	Abstract and further information provided by author. Gym attendance during the pooled intervention periods was high overall, with a mean of 14.5 visits and a median of 12 visits.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Computer‐generated random block sizes of four.
Concealment of Allocation	Low risk	Randomisation done centrally.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	1 dropout in the control group (3%).
Intention To Treat Analysis	Low risk	Intention‐to‐treat analysis.
Cointerventions Constant	Unclear risk	Drug therapy was allowed to change during the study.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Cross‐over design. Participants were randomly allocated in permuted blocks of six to an early or late intervention group by an independent investigator not involved in data analysis. Allocation was concealed by the use of opaque sealed envelopes. The data were analysed on an intention‐to‐treat basis. Treated at home for 4.5 hours over 3 weeks. Assessed at baseline, immediately after 1st and 2nd treatment, and at 12 weeks. Assessors were blinded.
Participants	76 participants in the cueing group and 77 in the control group. 1 dropout in the cueing group. Participants' mean age, 66.9 years (cueing), 67.2 years (control). Male/female ratio 48/28 (cueing), 40/37 (control). Hoehn and Yahr 2.7 (cueing), 2.8 (control). Mean duration of PD 7 years (cueing), 8 years (control). Inclusion criteria: diagnosis of idiopathic Parkinson's disease (defined by the UK Brain Bank Criteria), Hoehn and Yahr stage 2 to 4, showing mild to severe gait disturbance with score > 1 on the UPDRS item 29, stable drug usage, age 18 to 80 years. Exclusion criteria: undergone deep brain stimulation or stereotactic neurosurgery, had cognitive impairment (MMSE < 24), had disorders interfering with participation in cueing training, including neurological (stroke, multiple sclerosis, tumour), cardiopulmonary (chronic obstructive disorders, angina pectoris), and orthopaedic (osteoarthritis, rheumatoid arthritis, and back pain) conditions, had predictable and long‐lasting off periods (score 1 on item 37 and score > 2 on item 39 on UPDRS). Had participated in a physiotherapy programme 2 months before starting the trial.
Interventions	Cueing: cueing programme delivered at home over 3 weeks by 1 therapist in 9 sessions lasting 30 minutes. A prototype cueing device specifically developed for the study provided 3 rhythmical cueing modalities: 1. auditory (a beep delivered through an ear piece), 2. visual (light flashes delivered through a light‐emitting diode attached to a pair of glasses), 3. somatosensory (pulsed vibrations delivered by a miniature cylinder worn under a wristband). Participants tried all cueing modalities in the first week, but trained with their preferred modality. Cued practice was applied during a variety of tasks and aimed to improve step length and walking speed, prevent freezing episodes, and improve balance. Control: no training. Drug therapy was kept constant throughout the trial.
Outcomes	Posture and gait score. Gait and balance measures (including 10‐m test of walking, gait speed, step length, step frequency, functional reach, timed single leg and tandem stance, Freezing of Gait Questionnaire, Timed Up and Go Test. Activity measures (including Nottingham Extended Activities of Daily Living Index, Falls Efficacy Scale). Participation measures (including Parkinson's Disease Questionnaire‐39, Carer Strain Index). Falls diary. Assessments were performed at the same time of day when participant was in the 'on' phase approximately 1 hour after drug intake.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Permuted block size of 6.
Concealment of Allocation	High risk	Sealed envelopes.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	1 dropout in the cueing group (< 1%).
Intention To Treat Analysis	Low risk	The data were analysed on an intention‐to‐treat basis.
Cointerventions Constant	Low risk	All medication remained constant.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Cross‐over design. Method of randomisation not stated. Method of data analysis not described. 1 session per week for a total of 12 weeks. Assessed at baseline and immediately after 1st and 2nd treatments. Not stated whether the assessors were blinded.
Participants	10 participants in the martial arts group and 10 participants in the control group. One dropout from both groups. Mean age of participants 70 years in both groups. Male/female ratio, 7/2 (martial arts), 4/5 (control). Mean Hoehn and Yahr 2 (martial arts), 2.3 (control). No baseline characteristics given for dropouts. Inclusion criteria: maintenance phase of Parkinson's disease. No exclusion criteria.
Interventions	Martial arts: 1‐hour weekly Tai Chi training. Control: no treatment. Drug therapy not described.
Outcomes	Timed Up and Go Test. PDQ‐39. UPDRS. Hoehn and Yahr stage. Falls diary. Not stated when during the day examinations took place.
Notes	Abstract and poster only.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Unclear risk	Maintenance phase of Parkinson's disease.
Randomisation Method	Unclear risk	Randomisation method was not stated.
Concealment of Allocation	Unclear risk	Randomisation method was not stated.
Similarity at Baseline	Low risk
Withdrawals Described	Low risk	10% dropout
Intention To Treat Analysis	Unclear risk	Method of data analysis not described.
Cointerventions Constant	Unclear risk	Drug therapy was not described.
Blinded Assessors	Unclear risk	Not stated whether assessors were blinded.

Methods	Parallel group design. Random allocation using computer‐generated random list. Method of analysis not described. Treated as an outpatient for 36 hours over 3 months. Assessed at baseline and immediately after treatment. Assessors were blinded.
Participants	14 participants in the cueing group and 14 in the control group. No dropouts described. Participants' mean age, 70 years (cueing), 62 years (control); male/female 6/8 (cueing), 8/6 (control), mean Hoehn and Yahr score 2.4 (cueing), 2.3 (control). Duration of PD 7.5 years (cueing), 7.9 years (control). Inclusion criteria: diagnosis of idiopathic Parkinson's disease as per UK Brain Bank criteria, Hoehn & Yahr disease stages 2 and 3, stable Parkinson's disease medication for 1 month before baseline visit, ability to walk with headphones unaided for 30 minutes three times per week, absence of pre‐existing walking to music. Exclusion criteria: presence of dementia (MMSE < 26), presence of comorbidities that affect the ability to walk, hearing deficits.
Interventions	Cueing: walking for 30 minutes three times per week while listening to a battery of musical pieces. Music was self‐selected based on participant input and was cadence‐matched to the participant's ideal walking speed. Control: maintained their normal walking activity. Minor medication changes allowed, as deemed appropriate by team neurologist.
Outcomes	Gait and Balance Scale. UPDRS III. Adjusted PDQ‐39. Activities‐Specific Balance Confidence Scale. Not stated when examinations took place.
Notes	Abstract. Information on trial quality and data obtained from author.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	Low risk	Computer‐generated random list.
Similarity at Baseline	Low risk
Withdrawals Described	Unclear risk	No dropouts described.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Unclear risk	Minor medication changes allowed, as deemed appropriate by team neurologist.
Blinded Assessors	Low risk	Assessors were blinded to group allocation.

Methods	Parallel group design. Method: randomisation method not stated. Method of analysis not stated. Treated for 40 hours over 10 weeks. Assessed before and after treatment period. Not stated whether assessors were blinded.
Participants	12 participants in the physical therapy group and 12 in the control group. No dropouts described. Baseline characteristics not stated. Inclusion criteria: idiopathic Parkinson's disease, able to carry out activities of daily living independently, not part of any sports or physiotherapy treatment while participating in study, Hoehn & Yahr stage III. Exclusion criteria: secondary drawbacks (e.g. heart disease, arthritis, cognitive problems, not participating in experiments regularly).
Interventions	Physical therapy program: emphasis on tensional and supple exercises, chosen from Pito de Oto physical therapy and Donaron Rehabilitation centre, 5‐minute warm‐up of walking and exercises, 50 minutes of stretching and exercise, and 50minute cool‐down. Control group: no exercise. Both groups used the same doses of medications and were kept on the same medications throughout the trial.
Outcomes	Berg balance scale. Tinetti balance scale.
Notes	Translated from Farsi.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk	Eligibility criteria described.
Randomisation Method	Unclear risk	Method not stated.
Concealment of Allocation	Unclear risk	Randomisation method not stated.
Similarity at Baseline	Unclear risk	Baseline characteristics not stated.
Withdrawals Described	Unclear risk	Withdrawals not described.
Intention To Treat Analysis	Unclear risk	Analysis method not stated.
Cointerventions Constant	Low risk	No medication changes occurred during trial period.
Blinded Assessors	Unclear risk	Not stated whether assessors were blinded.

Methods	Parallel group design. Randomised by a 'random draw,' but concealment of allocation unclear. Method of analysis not described. Treated at home or in the community for 10.5 hours over 3 weeks. Assessed in the laboratory at baseline and immediately after treatment. Not stated whether the assessors were blinded.
Participants	15 participants in the cueing group, 11 participants in the exercise group, and 11 participants in the control group. No dropouts described. Participants' mean age, 69 (cueing), 74 (exercise), 71 (control); male/female 10/5 (cueing) 8/3 (exercise), 8/3 (control); Hoehn and Yahr 2.4 (cueing), 2.5 (exercise), 2.6 (control). Mean duration of PD 7.2 years (cueing), 5.4 years (exercise), 8.5 years (control). Inclusion criteria: idiopathic Parkinson's disease with significant gait deficits regarding speed, stride length, and cadence, but able to walk without physical assistance. No exclusion criteria.
Interventions	Cueing: Exercised for 30 minutes daily according to a prescribed program using rhythmic auditory stimulation (RAS). The RAS program consisted of walking on a flat surface, stair stepping, and stop‐and‐go exercises to rhythmically accentuated music at three different tempos. The tempos were labelled 'normal,' 'quick,' and 'fast.' Exercise (self‐paced therapy, SPT): performed their 300minute daily walking sessions without RAS, following the same training protocol and training exercises for the same length of time. Walking was divided equally into walking at normal pace, quick pace, and fast pace. Control: no treatment. Drugs stable during therapy.
Outcomes	Walk speed. Stride cadence. Stride length. EMG analysis on leg muscles. Footfall pattern. All testing done 90 to 120 minutes after first medication intake in morning.
Notes	3 arms to the trial: RAS, SPT, and no treatment. SPT vs RAS are examined in 'A comparison of physiotherapy techniques for participants with Parkinson's disease.' Cochrane review.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Eligibility Criteria	Low risk
Randomisation Method	High risk	Random draw.
Concealment of Allocation	Unclear risk	No information provided to allow assessment.
Similarity at Baseline	Low risk
Withdrawals Described	Unclear risk	No dropouts described.
Intention To Treat Analysis	Unclear risk	Method of analysis not described.
Cointerventions Constant	Low risk	Medication remained stable throughout study.
Blinded Assessors	Unclear risk	Not stated whether assessors were blinded.

Study	Reason for exclusion
Bergen 2002	No outcome measures relevant to our review.
Blackinton 2002	Initially identified as a suitable study for inclusion but was excluded because of the number of dropouts (47%; final number of participants analysed, n=8), which left the two groups unmatched by age and duration of Parkinson's disease.
Bridgewater 1997	Although this trial was designed as an RCT, after discussion with the authors it was discovered that the method of randomisation was compromised. 'In order of response to advertising, subjects were allocated alternately to group A (period of exercise, then no exercise) and group B (control, then complimentary exercise classes).' Although alternate allocation is an acceptable method of randomisation, the authors went on to change participants from group A to B if their personal circumstances dictated that they would be unavailable for the physiotherapy (e.g. if they were leaving the state on holiday). We feel that this compromised the randomisation procedure, and therefore excluded the trial.
Byl 2009	After email correspondence with the author, this trial was found out not to be randomised.
Chouza 2011	Whole body vibration technique not usually used by Physiotherapists.
Christofoletti 2010	Excluded as although the abstract for the study states 'randomised controlled trial,' after translation of the full paper, the study did not appear to be randomised; 'allocated to groups on convenience basis, following availability of participants at treatment site.' Attempted to contact author to clarify randomisation method but were unsuccessful.
Cianci 2010	Excluded as confounded because of use of rolling walker.
Comella 1994	The study did not report outcomes for the first assessment period and therefore has been excluded to prevent any bias of carryover or order effects.
Forkink 1996	No outcome measures relevant to our review.
Formisano 1992	Although this trial was controlled, the authors did not state that the allocation of participants into the two groups was random.
Gibberd 1981	The study did not report outcomes for the first assessment period and therefore has been excluded to prevent any bias of carryover or order effects.
Guo 2009	Multidisciplinary rehabilitation trail. Percentage component of physiotherapy was not specified, therefore unable to differentiate the contribution of physiotherapy to any change in the outcome measures.
Haas 2006	Excluded as the study was a randomised cross‐over over a couple of hours.
Hurwitz 1989	No outcome measures relevant to our review.
Kapur 2011	Whole‐body vibration technique not usually used by physiotherapists.
Katsikitis 1996	No outcome measures relevant to our review.
Kaut 2011	Whole‐body vibration technique not usually used by physiotherapists.
King 2009	Excluded as the study was a randomised cross‐over on the same day.
Knobl 2011	Not properly randomised, placed in groups.
Koc 2012	No patient numbers, methods, or data available; unable to make contact with authors.
Lee 2012	Upon discussion with the authors, it was discovered that the method of randomisation was compromised as all patients in the control arm received delayed treatment and were added into the experimental group.
Patti 1996	Multidisciplinary rehabilitation trail. Percentage component of physiotherapy was not specified, therefore unable to differentiate the contribution of physiotherapy to any change in the outcome measures.
Pohl 2003	Randomised multiple intervention cross‐over, over 4 consecutive days. Randomisation was of the sequence of the interventions, therefore not RCT.
Rochester 2011	Excluded, as the study was a randomised cross‐over over a couple of hours.
Sage 2009b	Upon contacting the author, it was found that the study was not properly randomised.
Stallibrass 2002	The method of therapy used － Alexander Technique － is not used by physiotherapists. Therefore this trial was excluded.
Tickle‐Degnen 2010	Multidisciplinary rehabilitation trail. Percentage component of physiotherapy was not specified, therefore unable to differentiate the contribution of physiotherapy to any change in the outcome measures.
Van Gerpen 2010	Excluded as confounded because of the use of a four‐wheeled walker.
Wade 2003	Multidisciplinary rehabilitation trail. Percentage component of physiotherapy was not specified, therefore unable to differentiate the contribution of physiotherapy to any change in the outcome measures.
Wells 1999	Although not stated in the text, upon personal communication with the author, this trial was determined to be an RCT. However the method of therapy used － osteopathic manipulative treatment － is not used by physiotherapists. Therefore this trial was excluded.
Yen 2011	No outcome measures relevant to our review.

Trial name or title	Exercise therapy for prevention of falls in people with Parkinson's disease: a randomised controlled trial.
Methods	Parallel group design. Randomisation was stratified by falls history (0‐10 falls in the previous 12 months/more than 10 falls in the previous 12 months) using a computer‐generated random number schedule with variable block sizes of 2 to 6. Randomisation was performed centrally by an investigator not involved in recruitment or assessments. Assessors were blinded.
Participants	230 participants. Inclusion criteria: diagnosis of Idiopathic Parkinson's disease. Adapted to their current antiparkinsonian medication for at least 2 weeks. Aged 40 years or over. Able to walk independently (with or without walking aid). Have a history of falls (at least one fall in the previous 12 months) or are at risk of falls. Exclusion criteria: Mini‐Mental State Examination score of < 24. Suffer from unstable cardiovascular disease or other uncontrolled chronic conditions that would interfere with the safety and conduct of the training and testing protocol or interpretation of the results.
Interventions	Exercise: 40‐ to 60‐minute program of home‐based balance and leg strength exercises three times a week for 6 months. Participants can choose to participate in a once‐a‐month exercise class (for 6 months) conducted by a physiotherapist in association with the local Parkinson's NSW/ACT Support Group or hospital. Participants will be provided with a booklet containing safety precautions, instructions, and photographs of exercises for use in exercise sessions at home, as well as information sheets detailing strategies for managing freezing. In addition, they will be provided with a logbook for recording exercises completed and any adverse effects of exercise. Participants will also receive standardised falls prevention advice and will be provided with a falls diary for recording falls. Control: will have standardised falls prevention advice and will be provided with a falls diary for recording falls.
Outcomes	Falls diary. Parkinson's Disease Falls Risk Score. Maximal muscle strength, knee extension (quadriceps). Step test component from the Berg Balance Scale. Short Physical Performance Battery. Freezing of Gait Questionnaire. SF12v2^TM health survey. Falls Efficacy Scale International Questionnaire. Habitual Physical Activity Questionnaire. PDQ‐39. Positive and Negative Affect Schedule (PANAS). Total cost. Tested at baseline and at the end of the 6‐month intervention period. *Data collected monthly.
Starting date	01/05/2008.
Contact information	Dr Colleen Canning (c.canning@usyd.edu.au). Discipline of Physiotherapy, Faculty of Health Sciences, The University of Sydney.
Notes	Australian New Zealand Clinical Trials Registry Number: ACTRN12608000303347.

Trial name or title	A randomised controlled trial (RCT) to evaluate use of auditory cueing device's (IACDs) on freezing and gait in people with Parkinson's disease (PD).
Methods	Randomly assigned using sealed, computer‐generated random numbers.
Participants	47 participants. Inclusion criteria: Parkinson's disease, medically stable, willing to give informed consent, freeze at least once per week (minimum score of 2 on item 3 of the FOGQ) for at least 2 seconds (minimum score of 1 on item 4 of FOGQ), MMSE score greater than 24. Exclusion criteria: attending physiotherapy at time of recruitment, unwilling to give informed consent, not medically stable, cognitive impairment (MMSE score less than 24), acute comorbidity that prevents mobility.
Interventions	Cross‐over trial. Cueing: iPod containing an auditory cue in the form of a continuous metronome beat, individualised to participants' walking frequency (less than 10%). Participants instructed to listen to cueing when performing any mobility‐related tasks for 8 days. Control: iPod shuffle with no music or metronome beat for 8 days.
Outcomes	Freezing of Gait Questionnaire. Timed Up and Go Test. Modified Falls Efficacy Scale. 10‐Metre Walk Test. Tested on days 8, 15, and 23 and at 3 months.
Starting date	Study not yet open for recruitment.
Contact information	Dr Emma K Stokes (estokes@tcd.ie).
Notes	On days 1‐8 of the trial, both groups given an iPod with some music on it to allow all participants to become familiar with the device. They will be instructed to use the device only when sitting at home, and that the device should not be turned on when walking or performing any mobility‐related or daily tasks. NCT00727467.

Trial name or title	Home‐based rehabilitation to reduce falls in people with Parkinson's disease (PD): a randomised controlled trial.
Methods	Parallel group design.
Participants	180 participants. Inclusion criteria: idiopathic Parkinson's disease, living in the community, Hoehn and Yahr stages 1 to 4. Exclusion criteria: suffer from cardiopulmonary, musculoskeletal, endocrine, or other medical condition that prevents safe participation in a home exercise program; participant or their carer/family are unwilling to have therapy and assessments in the home, are unable to communicate in English, have a dementia score MMSE score < 24, and unable to provide informed consent.
Interventions	Active intervention: 6‐week individualised home‐based rehabilitation program comprising a once‐weekly 1‐hour program delivered by a trained therapist, together with a once‐weekly 1‐hour self‐directed exercise program. The intervention is designed to provide participants with an integrated 'package' of evidence‐based therapy, including movement strategy training, strengthening, and falls education. Active control: 6‐week individualised home‐based 'life skills' program comprising a once‐weekly 1‐hour program delivered by a trained therapist, together with a once‐weekly self‐directed life skills home program. The active control is designed to provide education on taking medication, managing stress, driving, and other daily activities and will include content related to falls, physical exercise, and gait rehabilitation.
Outcomes	Fall frequency and injuries. UPDRS total and motor. PDQ‐39. EuroQOL. Tested at baseline, at 6 weeks, and at 12 months. *12 months only.
Starting date	01/08/2008
Contact information	Dr C Martin (cmartin@unimelb.edu.au). Centre for Health Exercise and Sports Medicine, School of Physiotherapy, The University of Melbourne.
Notes	ACTRN12608000390381.