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A systematic review and meta-analysis on effects of aerobic

exercise in people with Parkinson’s disease
1,3 ✉ 1,2 ✉
Kai Zhen1,2,4, Shiyan Zhang1,2,4, Xifeng Tao2, Gen Li2, Yuanyuan Lv and Laikang Yu

Previous studies have shown that aerobic exercise is an effective way to improve symptoms of Parkinson’s disease (PD). The aim of
this study [PROSPERO CRD42022340730] was to explore the effects of aerobic exercises on balance, gait, motor function, and
quality of life in PD patients. Searches were performed in PubMed, Web of Science, and EBSCO electronic databases. The Cochrane
risk assessment tool was used to evaluate the methodological quality of the included literature. From 1287 search records initially
identified, 20 studies were considered eligible for systematic review and meta-analysis. There was a significant effect of aerobic
exercise on improving timed up and go test [standardized mean difference (SMD), −0.41 (95% CI, −0.61 to −0.22), p < 0.00001],
Berg Balance Scale [0.99 (95% CI, 0.76 to 1.23), p < 0.00001], stride/step length [0.32 (95% CI, 0.03 to 0.61), p = 0.03], gait velocity
[0.49 (95% CI, 0.20 to 0.78), p = 0.0009], Unified Parkinson’s Disease Rating Scale Part-III [-0.40 (95% CI, −0.55 to −0.24), p < 0.00001],
and 6-minute walking test [0.35 (95% CI, 0.13 to 0.56), p = 0.002] in people with PD, but not in step cadence [−0.08 (95% CI, −0.43
to 0.27), p = 0.65] and Parkinson’s Disease Questionnaire-39 [−0.113 (95% CI, −0.39 to 0.13), p = 0.32]. Aerobic exercise had
beneficial effects in improving balance, gait (velocity and stride/step length), and motor function in PD patients. However, aerobic
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exercise had no significant associations with the step cadence and quality of life in PD patients.
npj Parkinson’s Disease (2022)8:146 ; https://doi.org/10.1038/s41531-022-00418-4

INTRODUCTION There is an increasing emphasis on complementary and

Parkinson’s disease (PD) is a progressive neurodegenerative alternative treatments without medication, such as exercise. There
disorder commonly affecting older adults worldwide1. The is growing evidence that exercise has benefits on neuroplasticity
manifestations of PD primarily include dysfunction of the and the ability of the brain to self-repair14. Animal studies have
somatomotor system (such as rigidity, bradykinesia, postural also found that exercise has a protective effect on the onset of PD
instability, gait dysfunction, and tremor)2,3. The disease course is symptoms15. Among the different types of exercise programmers,
usually accompanied by impairment of non-motor functions (such aerobic exercise is the most studied and is considered the best
as dementia, hyposmia, and gastrointestinal alterations)4–6. The option for improving people’s health throughout the lifespan16.
dysfunction caused by PD deprives patients of their ability to Studies have shown that aerobic exercise has neurorestorative
and neuroprotective effects, possibly by regulating neurotrophic
perform daily life activities and thus their independence7.
factors that support synaptogenesis and angiogenesis, inhibiting
Currently, PD affects about 0.3% of the general population and
oxidative stress, and improving mitochondrial function17. Aerobic
1–3% of the over-65 population, whose numbers will increase
exercise, such as treadmill training, walking, and dance, can
from 8.7 million to 9.3 million by 20308,9.
improve not only motor function but also gaits, balance, and
PD is usually treated with medication (levodopa, dopamine
quality of life in patients with moderate to severe PD18–20. Mehmet
agonizts) and surgery (deep brain stimulation)10. Pharmacother-
et al.21 reported that 14 patients with mild to moderate PD
apy is a common treatment approach that includes the
showed improvement in disease severity, balance, functional
optimization of levodopa-containing formulations and multiple mobility, and upper extremity motor function after receiving
drug dosing. However, as motor symptoms (dyskinesia, freezing) stationary recumbent bicycle training. To our knowledge, Mak
worsen, patients have a shorter and more limited response to et al.22 investigated the effects of long-term (≥12 weeks) aerobic
treatment (progressively weaker), requiring frequent doses of exercise on patients with PD, which included only eight
levodopa and its agonizts in advanced stages, and surgical randomized controlled trials (RCTs) and the number of included
intervention is also accompanied by safety concerns and side studies was quite small. Furthermore, due to the lack of short-term
effect. Significant improvements in PD symptoms have been aerobic exercise, the effect of aerobic exercise on PD patients
inconsistent after taking levodopa and related medications, and cannot be fully reflected. Therefore, further studies with more
patients must face severe motor and cognitive impairments11. included studies are needed. Another study evaluated the effects
Conventional pharmacotherapy can also reduce an individual’s of resistance training (RT), endurance training (ET), and other
balance and walking ability and increase the risk of falls12. intensive exercise modalities (OITM) on patients with PD23.
Additionally, two novel therapeutic approaches, neurotrophic However, the authors included studies in which control group
factor therapy and cell transplantation, rely heavily on highly participants also received exercise interventions such as 60–80%
invasive stereotaxic surgery, so these strategies do not provide a heart rate reserve (HRR) voluntary exercise (two studies), and
perfect treatment for PD patients13. upper and lower limbs, stretching, and gait training (one study). In

1
Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China. 2Department of Sports Performance, Beijing Sport
University, Beijing, China. 3China Institute of Sport and Health Science, Beijing Sport University, Beijing, China. 4These authors contributed equally: Kai Zhen, Shiyan Zhang.
✉email: sunflowerlyy@bsu.edu.cn; yulaikang@126.com

Published in partnership with the Parkinson’s Foundation

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Fig. 1 PRISMA flowchart of study selection.

addition, one of the included studies used healthy adults as a normal daily activities, and conventional medication. Intervention
control group, which may have had some impact on their findings. duration ranged from 3 weeks to 6 months. Nine included studies
Therefore, we conducted a comprehensive systematic review and used the BBS as the outcome24–32, and ten studies reported TUG
meta-analysis of RCTs to explore the effects of aerobic exercises data to assess the balance24,28,30,31,33–38. Thirteen studies reported
on balance, gait, motor function, and quality of life in PD patients. the data from UPDRS-III, including 16 outcomes24,27–29,31,33,36–42.
We extracted nine data for eight studies on 6MWT24,28,31–33,35,39,42,
but only six and four trials reported data on gait24,25,31,34,36,43 and
RESULTS PDQ-3933,37,39,42, respectively.
Study selection
As shown in Fig. 1, a total of 1287 search records were Risk of bias
preliminarily retrieved, and 14 records were identified through Cochrane risk assessment tool was used to evaluate the
other sources. After excluding the duplicates, 843 studies methodological quality of the included literature, mainly from
remained, and 793 studies were not eligible for inclusion through six aspects: selection bias, performance bias, detection bias,
the title and abstract screening. Thirty studies were excluded by attrition bias, reporting bias, and other bias. As shown in Fig. 2, the
reading the full text of 50 studies: (1) the experimental group included studies were graded as low quality, moderate quality, or
combined with other treatments (n = 8); (2) no control group high quality based on the following criteria: (1) trials were
(n = 19); and (3) the data could not be extracted (n = 3). Finally, considered low quality if either randomization or allocation
20 studies examining the effect of aerobic exercise on balance, concealment was assessed as a high risk of bias, regardless of
gait, motor function, and quality of life in PD patients were the risk of other items; (2) trials were considered moderate quality
considered eligible for systematic review and meta-analysis. if they did not meet criteria for high or low risk; (3) trials were
considered high quality when both randomization and allocation
Study characteristic concealment was assessed as a low risk of bias, and all other items
were assessed as low or unclear risk of bias in a trial44. One study
The main characteristics of the participants and interventions were
provided evidence of low quality, one study provided evidence of
shown in Table 1. The included studies involved 450 participants
moderate quality, and 18 studies provided evidence of high
in the 23 exercise groups and 352 participants in the 20 control
quality. Publication bias was assessed visually by inspecting the
groups. Most participants with mild to moderate PD included 18 funnel plot (Fig. 3).
trials with 744 patients (Hoehn and Yahr stage I to III) and 2 trials
with 58 patients (Hoehn and Yahr stage I to IV). All included
studies reported aerobic interventions, such as treadmill training, Meta-analysis results
walking, cycling, dancing, and other types of aerobic training. The Effects of aerobic exercise on TUG in people with PD. Ten
control group had no other interventions, including usual care, studies24,28,30,31,33–38 provided data for TUG. It was found that

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 Table 1. Characteristics of studies included in this meta-analysis.

Study Country Sample size Age(y) Stage of disease Disease Intervention Characteristics of Interventions Outcome measures
duration (y)

Sage (2009) NR IG = 13 IG: 65.1 (9.3) UPDRS, IG: 3.2 (2.9) IG: aerobic intervention 30 min/session, 60–75% HRmax, two UPDRS-III, TUG, Gait
CG = 15 CG: 68.6 (8.7) IG: 22.2 (8.1) CG: 2.5 (2.2) CG: regular activity sessions per week for 10–12 weeks
CG: 21.8 (7.2)
Cannning (2012) Australia IG = 10 IG: 60.7 (5.9) Total: H&Y stage IG: 6.1 (4.0) IG: treadmill walking 20-40 min/session, 60–80% of the UPDRS-III, 6MWT,
CG = 10 CG: 62.9 (9.9) 1–3 CG: 5.2 (4.1) CG: usual care average 6-min walk test speed, four PDQ-39
sessions per week for 6 weeks
Arfa-Fatollahkhani (2019) Iran IG = 11 IG: 60.63 (9.36) Total: H&Y stage IG: 8.89 (5.14) IG: treadmill walking 30 min/session, 60%HRmax, two sessions TUG, 6MWT
CG = 9 CG: 1.5–2.5 CG: 8.50 (6.34) CG: usual care per week for 10 weeks
61.55 (8.57)
Solla (2019) Italy IG = 10 IG: 67.8 (5.9) H&Y, IG: 2.1 (0.6) IG: 4.4 (4.5) IG: dance 90 min/session, two sessions per week for UPDRS-III, 6MWT,
CG = 10 CG: 67.1 (6.3) CG: 2.3 (0.4) CG: 5.0 (2.9) CG: usual care 12 weeks BBS, TUG, Gait
Wan (2021) China IG = 20 IG: 64.95 (7.83) Total: H&Y stage IG: 3.63 (1.52) IG: Qigong 60 min/session, 70–80% HRmax, four TUG, Gait
CG = 20 CG: 1–4 CG: 3.25 (1.7) CG: regular medication sessions per week for 12 weeks
67.03 (7.47)

Published in partnership with the Parkinson’s Foundation

Hashimoto (2015) Japan IG = 15 IG: 67.9 (7.0) UPDRS, IG: 6.3 (4.6) IG: dance 60 min/session, one session per week for BBS, TUG
CG = 14 CG: 69.7 (4.0) IG: 42.7 (13.9) CG: 7.8 (6.2) CG: normal lives 12 weeks
CG: 33.4 (14.2)
Lee (2018) Korea IG = 25 IG: 65.8 (7.2) Total: H&Y stage IG: 4.5 (3.3) IG: dance 60 min/session, 60–75% HRmax, two UPDRS-III, BBS
CG = 16 CG: 65.7 (6.4) 1–3 CG: 4.4 (3.0) CG: normal lives sessions per week for 8 weeks
Hackney (2009) US IG-1 = 14 IG-1: 68.2 (1.4) Total: H&Y stage IG-1: 6.9 (1.3) IG-1: tango 60 min/session, 60–75% HRR, two UPDRS-III, BBS
IG-2 = 17 IG-2: 66.8 (2.4) 1–4 IG-2: 9.2 (1.5) IG-2: waltz/foxtrot sessions per week, completing TUG, 6MWT, Gait
CG = 17 CG: 66.5 (2.8) CG: 5.9 (1.0) CG: no intervention 20 sessions within 13 weeks
Altmann (2016) US IG = 11 IG: 62.8 (8.6) Total: H&Y stage NR IG: aerobic exercise 20–45 min/session, 50–75% HRR, three UPDRS-III
CG = 10 CG: 67.8 (9.8) 1–3 CG: normal activities sessions per week for 16 weeks
Cugusi (2015) Italy IG = 10 IG: 68.1 (8.7) Total: H&Y stage IG: 7.0 (2.0) IG: walking 60 min/session, 60–80% HRR, two UPDRS-III, BBS,
K. Zhen et al.

CG = 10 CG: 66.6 (7.3) 1–3 CG: 7.0 (4.0) CG: conventional care sessions per week for 12 weeks TUG, 6MWT
Ganesan (2014) US IG = 20 IG: 57.6(9.1) Total: H&Y stage IG: 5.7 (3.9) IG: treadmill training 30 min/session, four sessions per week UPDRS-III, BBS
CG = 20 CG: 59.1 (6.8) 1–3 Cg: 5.5 (3.4) CG: only stable dosage for 4 weeks
Schenkman (2017) US IG-1 = 39 IG-1: 64 (9) Total: H&Y stage Total: <5 IG-1: treadmill exercise IG-1: 40–50 min/session, 80–85% HRmax, UPDRS-III
IG-2 = 42 IG-2: 63 (10) 1–2 IG-2: treadmill exercise four sessions per week for 24 weeks
CG: N = 38 CG: 64 (10) CG: wait-list control IG-2: 40–50 min/session, 60–65% HRmax,
four sessions per week for 24 weeks
Cakit (2007) Turkey IG = 21 Total: 71.8 (6.4) Total: H&Y stage Total: 5.58 (2.9) IG: treadmill training 30 ± 5 min/session, walking at the BBS
CG = 10 2–3 CG: no intervention maximum speed, for 8 weeks
Protas (2005) US IG = 9 IG: 71.3(7.4) Total: H&Y stage IG: 7.1 (5.1) IG: walking 60 min/session, walking at the fastest, Gait
CG = 9 CG: 73.7 (8.5) 2–3 CG: 8.1 (4.4) CG: no intervention self-selected speed, three sessions per
week for 8 weeks
Thaut (1996) US IG = 11 IG: 74.0 (3.0) IG: 2.6 (NR) IG: 5.4 (3.0) IG: walking 30 min/session, 60–120 steps/min, one BBS, Gait
CG = 11 CG: 71.0 (8.0) CG: 2.5 (NR) CG: 8.5 (4.0) CG: normal daily session per week for 3 weeks
activities
van der Kolk (2019) Netherlands IG = 65 IG: 59.3 (8.3) Mild stage IG: 15.1 (4.0) IG: aerobic exercise 30–45 min/session, 50–80% HRmax, three UPDRS-III, TUG,
CG = 11 CG: 59.4 (8.3) Total: H&Y stage CG: 16.1 (4.5) CG: active control group sessions per week for 24 weeks 6MWT, PDQ-39
<2
Nadeau (2014) Canada IG-1 = 11 IG-1: 60.1 (6.8) IG-1: 1.95 (0.15) NR IG-1: treadmill walking 60 min/session, 60–80% VO2peak, three UPDRS-III, 6MWT,

npj Parkinson’s Disease (2022) 146

IG-2 = 12 IG-2: 64.0 (6.6) IG-2: 1.92 (0.20) IG-2: treadmill walking sessions per week for 24 weeks PDQ-39
CG = 11 CG: 64.3 (5.6) CG: 1.86 (0.23)
3
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compared with the control group, aerobic exercise had a
Outcome measures

PD Parkinson’s disease, EG experimental group, IG control group, M male, NR no report, N number, H&Y Hoehn and Yahr, UPDRS unified Parkinson’s disease rating, UPDRS-III unified Parkinson’s disease rating scale
part-III, TUG timed up and go test, BBS Berg balance scale, 6MWT 6-minute walking test; Data were presented as mean (standard deviation), HRmax maximum heart rate, HRR heart rate reserve, VO2peak peak
significant effect on improving TUG in people with PD [SMD,

90 min/session, 60–70% HRmax or 6–12 UPDRS-III, TUG,

UPDRS-III, TUG
−0.41 (95% CI, −0.61 to −0.22), p < 0.00001, I2 = 22%, Fig. 4].

60 min/session, 80% HRmax, five sessions BBS, 6MWT

on Brog scale, two sessions per week for PDQ-39
Effects of aerobic exercise on BBS in people with PD
Nine studies24–32 provided data for BBS. It was found that
compared with the control group, aerobic exercise had a
significant effect on improving BBS in people with PD [SMD,
0.99 (95% CI, 0.76 to 1.23), p < 0.00001, I2 = 18%, Fig. 5].
three sessions per week for 12 weeks
40–60 min/session, 60–80% VO2max,
Characteristics of Interventions

Effects of aerobic exercise on gait in people with PD

Six studies24,25,31,34,36,43 provided data for stride/step length and
gait velocity, and five studies25,31,34,36,43 provided data for step
CG: a wait-listed control per week for 5 weeks cadence. It was found that compared with the control group,
aerobic exercise had a significant effect on improving gait in
people with PD. Specifically, aerobic exercise significantly
increased the stride/step length [SMD, 0.32 (95% CI, 0.03 to
0.61), p = 0.03, I2 = 0%, Fig. 6] and the gait velocity [SMD, 0.49
CG: active control group 24 weeks

(95% CI, 0.20 to 0.78), p = 0.0009, I2 = 30%, Fig. 6] in people with

PD. However, aerobic exercise had no significant associations with
the step cadence in people with PD [SMD, −0.08 (95% CI, −0.43 to
0.27), p = 0.65, I2 = 0%, Fig. 6].
CG: normal physical

IG: Wuqinxi Qigong

CG: control group
IG: aerobic group

Effects of aerobic exercise on UPDRS-III in people with PD

Thirteen studies24,27–29,31,33,36–42 provided data for UPDRS-III. It
Intervention

was found that compared with the control group, aerobic

IG: cycling

exercise had a significant effect on reducing UPDRS-III in people

exercise
activity

with PD [SMD, −0.40 (95% CI, −0.55 to −0.24), p < 0.00001,

I2 = 27%, Fig. 7].
IG: 23.00 (10.42) CG: 5.17 (4.26)

CG: 70.0 (5.59) IG: 25.05 (17.45) CG: 7.76 (4.55)

IG: 3.91 (2.85)

IG: 6.93 (4.09)

Effects of aerobic exercise on 6MWT in people with PD

CG: 7.3 (2.21)
IG: 7.5 (2.16)
duration (y)

Eight studies24,28,31–33,35,39,42 provided data for 6MWT. It was

Stage of disease Disease

found that compared with the control group, aerobic exercise had
a significant effect on improving 6MWT in people with PD [SMD,
0.35 (95% CI, 0.13 to 0.56), p = 0.002, I2 = 24%, Fig. 8].
CG: 2.4 (0.51)

Effects of aerobic exercise on PDQ-39 in people with PD

Four studies33,37,39,42 provided data for PDQ-39. It was found that
CG: 26.77

CG: 26.79

CG: 67.5 (4.28) 2.4 (0.51)

IG: 70.6 (4.10) H&Y, IG:
IG: 66.76 (5.98) UPDRS,

IG: 67.57 (3.95) UPDRS,

(13.14)

(20.79)

aerobic exercise had no significant associations with PDQ-39 in

people with PD [SMD, −0.13 (95% CI, −0.39 to 0.13), p = 0.32,
I2 = 0%, Fig. 9].
67.85 (8.50)

Adverse events
Adverse events related to exercise intervention were reported for
Sample size Age(y)

1 of 20 studies (5.0%). Eleven adverse events were reported.

CG:

Specifically, seven adverse events occurred in the intervention

oxygen uptake, VO2max maximal oxygen consumption.

group and four adverse events occurred in the control group.

Further, the majority of adverse events were not associated with
CG = 15

CG = 20

CG = 24
IG = 20

IG = 20

Netherlands IG = 25

the exercise intervention, meaning that aerobic exercise was safe

for PD patients.

Follow-up effect
Country

Canada

Three studies reported on follow-up periods of 6 weeks to

China

6 months. Two studies showed that the effect of aerobic exercise

on PDQ-39 was only significantly different at follow-up (6 weeks
and 2 months, respectively) compared to post-exercise test-
ing43,45. One study reported significant differences in UPDRS-III
Table 1 continued

after 6 months of follow-up, suggesting a persistent effect of

aerobic exercise on motor symptoms in PD patients43.
Sacheli (2019)

Tollár (2019)
Li (2022)

DISCUSSION
Study

Twenty studies examining the effect of aerobic exercise on

balance, gait, motor function, and quality of life in PD patients

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Fig. 2 Results of Cochrane risk of bias tool. Above: Risk of bias summary: review authors’ judgments about each risk of bias item for each
included study. Below: Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included
studies.

were considered eligible for systematic review and meta-analysis. between the upper and lower limbs, resulting in an improved
However, the included studies were all RCTs of aerobic exercise balance in daily living tasks with greater complexity49.
intervention, which could not be completely blinded. Previous Creaby et al.46 emphasized that PD patients have a slower gait
study has shown that results of a trial using the best possible velocity and are at greater risk of falls and complications.
methods may still be at risk of bias. For example, blinding may not Therefore, improving gait is important for preventing falls in PD
be feasible in many non-drug trials, and it would not be patients. Our meta-analysis showed that aerobic exercise had a
reasonable to consider the trial as low quality because of the positive effect on gait velocity and stride/step length, while
absence of blinding44. Therefore, in the quality evaluation process, aerobic exercise had no significant associations with step cadence
18 studies were considered to be of high quality, which in people with PD, which was consistent with previous studies,
contributed to strengthen our results and conclusions. showing that 4 to 24 weeks of aerobic exercise significantly
This systematic review and meta-analysis indicated that aerobic improved both gait velocity and stride/step length39,47–49. Aerobic
exercise had the potential to improve balance, gait (velocity and exercise can promote postural responses and decoupling of pelvis
stride/step length), and motor function in people with PD and shoulder girdle movements, thereby reducing axial stiffness.
compared to placebo or no intervention. In addition, our results Improvements in trunk control may contribute to improvements
showed no significant heterogeneity in TUG (I2 = 22%), BBS in balance, walking, and posture50,51. However, there is not much
(I2 = 18%), stride/step length (I2 = 0%), step cadence (I2 = 0%), evidence to support the effect of aerobic exercise on step
6MWT (I2 = 24%), and PDQ-39 (I2 = 0%), and low heterogeneity in cadence. Nadeau et al.39 reported that a longer aerobic exercise
UPDRS-III (I2 = 27%) and gait velocity (I2 = 30%), indicating on a treadmill (24 months) was able to promote improvements in
consistent results from the included studies. Therefore, we did step cadence, while a shorter protocol (4 months) did not achieve
not perform subgroup analysis or sensitivity analysis. However, this benefit. Therefore, the effect of aerobic exercise intensity and
there was insufficient data to support the effectiveness of aerobic duration on gait are unclear and more research is needed.
exercise in improving quality of life after post-exercise testing, but Motor symptoms of PD include tremor, bradykinesia, hypoki-
two studies40,43 showed improved quality of life in PD patients at nesia, bradykinesia, rigidity, gait disturbances, and postural
2-week and 2-month follow-up, respectively, which suggested disturbances. The severity of the motor signs is usually assessed
that the effect of aerobic exercise on the quality of life of PD by UPDRS-III52. Dyskinesia progresses rapidly, with UPDRS-III scores
patients may take a long time to be observed. ranging from 1.5 to 8.9 per year53,54. In our study, aerobic exercise
Most people with PD suffer from impairments in maintaining a had a significant effect on reducing UPDRS-III in people with PD,
balanced and stable posture. Sometimes, they fall, which can be which was consistent with a previous meta-analysis, showing that
dangerous in normal life. Statistics showed that falls affect more aerobic exercise reduced UPDRS-III significantly55,56. Previous
than 50% of PD patients46,47. BBS and TUG are commonly used to studies revealed that aerobic walking was safe, well-tolerated,
assess posture balance and control39,48. Our study provided and improved aerobic fitness, motor function, and quality of life in
evidence that aerobic exercise improved BBS and TUG in PD people with mild to moderate PD57,58. Changes in UPDRS-III
patients, as well as enhanced physical control and falls prevention demonstrate the positive effects of aerobic intervention, as UPDRS
in daily life, which was consistent with a previous study, showing is considered the gold standard for such analyses59. Carvalho
that the benefits of Nordic walking lie in improved coordination et al.60 showed that both aerobic exercise and strength training

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Fig. 3 Funnel plot. a Funnel plot for TUG. b Funnel plot for BBS. c Funnel plot for gait. d Funnel plot for UPDRS-III. e Funnel plot for 6MWT.
f Funnel plot for PDQ-39.

improved motor symptoms in PD patients (UPDRS-III was 35 and had a positive effect on enhancing balance function and walking
27.5%, respectively), while aerobic exercise was better. ability58,61,62.
The 6MWT provides a measure of walking endurance61. The test The PDQ-39 has 39 items, designed by Peto et al.63. The higher
was conducted in a 100-m long corridor where participants were the score, the lower the quality of life. The PDQ-39 has eight
asked to walk as fast as possible for 6 min, and the total walking subscales, namely mobility (ten items), activities of daily living (six
distance (m) was measured by the evaluator. Our meta-analysis items), emotional well-being (six items), stigma (four items), social
showed that aerobic exercise had a positive effect on improving support (three items), cognition (four items), communication (four
6MWT in people with PD, which was consistent with a previous items), and bodily discomfort (three items)64–67. PDQ-39 is
study, showing that walking improved regardless of the duration currently recognized as the most comprehensive and widely used
specific scale for evaluating the quality of life of PD patients65.
of aerobic exercise58. In addition, studies have shown that aerobic
However, most studies have shown no significant improvement in
exercise improved the ability of PD patients to deal with
the quality of life of PD patients after aerobic exercise intervention,
behaviorally complex motor tasks, while aerobic exercise also which was consistent with our study. de Oliveir et al.68 conducted

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Fig. 4 Meta-analysis results of the effect of aerobic exercise on TUG in people with PD. The pooled estimates were obtained from fixed
effects analysis. Diamonds indicated the effect size of each study summarized as SMD. The size of the shaded squares was proportional to the
percentage weight of each study. Horizontal lines represented the 95% CI and the vertical line represented the overall effect.

Fig. 5 Meta-analysis results of the effect of aerobic exercise on BBS in people with PD. The pooled estimates were obtained from fixed
effects analysis. Diamonds indicated the size of the effect of each study summarized as SMD. The size of the shaded square was proportional
to the percentage weight of each study. Horizontal lines represented the 95% CI and the vertical dashed line represented the overall effect.

a meta-analysis including ten studies with 411 PD patients and transcriptional regulator peroxisome proliferator-activated recep-
concluded that there was no significant improvement in PDQ-39 tor gamma (PPARγ) coactivator 1α (PGC1α), and regulation of
after aerobic exercise compared to the usual care or placebo dopamine turnover74. A peripheral indicator of neurogenesis is
group. However, Chen et al.69 reported that aerobic exercise could BDNF, which helps to support neuronal growth and survival71–73.
improve the quality of life in PD patients, but different scales such Decreased levels of neurotrophic factors, mainly BDNF and its
as the PDQ-39 scale, Parkinson’s disease quality of life ques- receptors, are among the most common physiological changes in
tionnaire (PDQL), EuroQol (EQ-5D) and other types of scales were neurodegenerative diseases such as PD75–78. A previous study has
used to assess the quality of life. Therefore, since different scales shown that aerobic exercise induced an increase in BDNF levels,
have different criteria, there may be evaluation bias. It has been protected dopaminergic neurons, and was involved in the
reported that PD patients are better able to concentrate, activation and recovery of motor function79. In addition, Zoladz
remember, and recall information after the aerobic intervention, et al.80 also reported that aerobic exercise can be therapeutically
which may have a positive impact on quality of life70. In this meta- effective by increasing BDNF levels. Previously, it was suggested
analysis, studies that met the inclusion criteria reported limited that aerobic intervention lasting at least 12 weeks for a duration of
data on quality of life. Therefore, more research on the quality of 40 min is the most effective exercise strategy for increasing BDNF
life of PD patients using the same scale should be conducted, and levels81. A meta-analysis also showed that aerobic exercise
data collection and research analysis should be emphasized in the increased BDNF levels in people with neurological disorders
future. compared to the usual care or placebo group. Upregulation of
PD is a progressive neurodegenerative disease caused by the BDNF is considered desirable because it is associated with
progressive loss of neurons and protein deposition in the brain enhanced plasticity-related processes such as dendritic growth,
that exhibits altered physicochemical properties71–73. Aerobic neurogenesis, and long-term potentiation of neurons82.
exercise has been associated with neuroprotective effects in the Furthermore, aerobic exercise, as an effective non-drug therapy,
nigrostriatal dopaminergic system, so as to improve many motor not only promotes physical fitness in PD patients, but also
and non-motor Parkinson’s symptoms, and the proposed mechan- improves motor learning in daily activities by enhancing the
isms that link physical activity to neuroprotective effect are an plasticity of exercise-related structures83. Rosenfeldt et al.84
increase in serum urate, an increased release of neurotrophic reported that 8 weeks of aerobic exercise altered various signaling
factors [e.g., brain-derived neurotrophic factor (BDNF) and glial pathways in the central nervous system, modulated cognitive or
cell-derived neurotrophic factor (GDNF)], upregulation of the physiological processes, and controlled the sense of smell in PD

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Fig. 6 Meta-analysis results of the effect of aerobic exercise on gait in people with PD. The pooled estimates were obtained from fixed
effects analysis. Diamonds indicated the size of the effect of each study summarized as SMD. The size of the shaded square was proportional
to the percentage weight of each study. Horizontal line represented the 95% CI and the vertical dashed line represented the overall effect.

patients. Retrospective studies have also found that moderate- life in PD patients. Therefore, in future studies, these findings
intensity to vigorous-intensity aerobic exercise can prevent should shed new light on the very important issue that aerobic
PD85,86. Aerobic exercise is a very popular functional recovery exercise may improve balance, gait, and motor function in
treatment that has positive effects on motor function, quality of patients with PD.
life, cognition, and mood in PD patients. Therefore, functional
improvements, motor symptoms, balance, and gait improvements
can be explained by the cellular and biochemical responses
METHOD
induced by aerobic exercise, which acts as a regulator of
neurogenesis and neuronal plasticity and is neuroprotective in This systematic review and meta-analysis were conducted
various cortical regions87–90. following the guidelines of the Cochrane Selection Manual91 and
This systematic review and meta-analysis also had several the Preferred Reporting Items for Systematic Reviews and Meta-
limitations that should be noted. Firstly, the included studies were Analysis (PRISMA)92. The protocol for this systematic review has
all RCTs of aerobic exercise intervention, which could not be been registered on PROSPERO (CRD42022340730).
completely blinded. Therefore, in the quality evaluation process,
subjective factors will cause a certain degree of deviation. Search strategy
Secondly, the scale for assessing the quality of life in patients
with PD is not unique, we chose PDQ-39 as a data source, resulting For this systematic review and meta-analysis, we searched
in fewer data included. There may be some bias in assessing the through PubMed, Web of Science, and EBSCO electronic
impact of aerobic exercise on quality of life. Finally, we did not databases from the inception of indexing until September 5,
analyze the longer-term effect of aerobic exercise on PD as only a 2022. All studies on aerobic exercise and PD were searched using
few included studies reported follow-up data in the meta-analysis. the following MESH terms and keywords: aerobic exercise and
Our analysis indicated that aerobic exercise had beneficial Parkinson’s disease. We also hand-searched reference lists of all
effects in improving balance, gait (velocity and stride/step length), identified studies. We excluded studies based on the review of the
and motor function in PD patients. However, aerobic exercise had title, abstract, and full text. Two authors (KZ and SZ) conducted the
no significant associations with the step cadence and quality of process independently using a standardized form. In case of any

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Fig. 7 Meta-analysis results of the effect of aerobic exercise on UPDRS-III in people with PD. The pooled estimates were obtained from
fixed effects analysis. Diamonds indicated the size of the effect of each study summarized as SMD. The size of the shaded square was
proportional to the percentage weight of each study. Horizontal line represented the 95% CI and the vertical dashed line represented the
overall effect.

Fig. 8 Meta-analysis results of the effect of aerobic exercise on 6MWT in people with PD. The pooled estimates were obtained from fixed
effects analysis. Diamonds indicated the size of the effect of each study summarized as SMD. The size of the shaded square was proportional
to the percentage weight of each study. Horizontal line represented the 95% CI and the vertical dashed line represented the overall effect.

Fig. 9 Meta-analysis results of the effect of aerobic exercise on PDQ-39 in people with PD. The pooled estimates were obtained from fixed
effects analysis. Diamonds indicated the size of the effect of each study summarized as SMD. The size of the shaded square was proportional
to the percentage weight of each study. Horizontal line represented the 95% CI and the vertical dashed line represented the overall effect.

discrepancies between the two authors, a third author (LY) was should use PD patients as subjects; and (4) should use balance,
involved in the discussion until a consensus was made. gait, motor function, or quality of life as the outcome measure.
Non-English language publications, animal model publications,
Eligibility criteria reviews, and conference articles were excluded from the analysis.
We included studies that satisfied the following criteria: eligible
studies (1) should be RCTs; (2) should include both an intervention Data extraction
and control group with the only difference between them being Two authors of the review performed the data extraction
the addition of aerobic exercise in the intervention group; (3) independently using the same standardized form created in

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 K. Zhen et al.
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