One year outcome of physical therapy on Parkinson disease:

A global new way.

Mingming Zhao#123, Zhengming Lia4, Zhixin Wu5, Chong Zhang6, Yu chen4, Mingsheng Zhang*2

1.Southern Medical University, Guangzhou, Guangdong, 510515, China.

2.Department of Rehabilitation Medicine, Guangdong Geriatric Institute, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou,510080, China.

3.Department of Neurology, Jiangbin Hospital, Guangxi Zhuang Autonomous Region, Nanning,530021, China.

4. Department of Rehabilitation, Jiangbin Hospital, Guangxi Zhuang Autonomous Region, Nanning,530021, China.

5. Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan,528000, China

6. The first Affiliated Hospital Of GuangXI University Of Chinese Medicine, Nanning,530000, China.

* Corresponding author.

a Co-corresponding author

# First author

Abstract:

Background

Parkinson’s disease (PD) seriously impact patients’ normal lives by movement and balance disorder. Most of PD patients decrease their exercise to avoid falls, especially in China, to avoid motor dilemma more patients hold traditional health maintenance prefer staying quietly, only few PD patients could do regular and helpful exercise. Therefore, these false behaviors notably accelerate PD progression, worsen functional decline and the quality of daily life, which is generally believed to be the cause of caregiver distress increasing, and bring earlier nursing care. Additionally, abnormal gestures of the trunk which are the characteristic features of Parkinson’s disease (PD) impair not only the ability of motor and balance ,but also cardiovascular function. The literature suggests that sports may be considered to improve quality of life in PD patients. Thus, we design this study according to popular fitness-training program of “Dry-land swimming”, which as an aerobic exercise could improve heart function, coordination variability and stability of the body. Moreover, paraspinal muscle especially Multifidus supplies strong power to control the stability of the spine. Meanwhile paraspinal muscles of PD patients become gradually degeneration. In this study we describe the effect of Coordination and Manipulation Technology (CNMT) on motor deficits and left ventricularejection fraction (LVEF) of 36PD patients for one year therapy.

Methods and Findings

All PD patients (n=36) were randomly divided into two groups, the treated group (n=22) were given CNMT for one hole year. Clinical characteristics of treated group were compared with a control group (n=14) without CNMT. We calculated biochemical test results, Berg Balance Score (BBS), time of Timed Up And Go Test (TUGT), Unified Parkinson Disease Rating Scale (UPDRS) and left ventricular (LV) and ejection fraction (LVEF).

Patients in treated group showed a significantly higher score of Berg Balance Score (BBS, P<0.001) and shorter time of Timed Up And Go Test (TUGT) compared with the control group. After a whole year training, in all cases compared with pretherapy, notable scores changes conformed to patients in CNMT group showing greater improvement (Including four segments of UPDRS: part I addresses mental dysfunction and mood; part II assesses physical function status of daily living; part III evaluates motor impairment). Except for CPL, other parameters(CCA, OCA,OPL) measured by balancing instrument showed significantly declined (P<0.01), which had the similar clinical implications as BBS increased (η2=0.41 , P<0.01 ). CNMT group showed significantly elevated in LVEF (t=5.945, P<0.01).No serious adverse effects were encountered during or after the therapy progress. Overall, motor functions improved within 1 year’s CNMT therapy together with LVEF.

Several limitations involved in this study, such as small size of sample and short training duration. Meanwhile, as a pilot study our results need to be confirmed in further larger trails. The detailed mechanism of improvement of mobility, balance skill and heart function after

CNMT had not been described nor demonstrated in this pilot study.

Conclusion

CNMT therapy provided sustained and effective benefits of mobility and balance skill to PD patients over a 1-year period.

This study was conducted with institutional review board approval and in compliance with local goverment regulations. Trial identification number: S201311-03.

1. Introduction

Parkinson’s disease (PD) with mobility and mortality climbing is common seen as a progressively and prevalently neurodegenerative disease, which seriously impacts patients’ normal lives by movement and balance disorder [2-5]. PD affects up to 2 million Americans which suggested a similar prevalence in China, the overwhelming majority of whom are aged 60 and older[4-6].The substantia nigra progressivly loss dopaminergic neurons then directly results in clinical symptoms including bradykinesia, rigidity, distal resting tremor, asymmetric onset and non-motor symptoms[7, 8]. In fact, not only motor function is significantly influenced, cardiovascular function also becomes involved [9,10].To be paid More attention on is many patients have to rely on a long term care facility (LTC) as PD develops, both PD patients and government should pay enormous cost to maintain PD patients’ daily lives. The economic burden soars every year together with the aging of population all over the world [5,6] and public health challenge become greater. However, it is urgently required but fails to find out new strategy to reverse this increasing trend. Traditional dopamine replacement therapy is still the most effective symptomatic strategy to extend the life span of PD patients. Despite this, it is reported the therapeutic effects reduce after long term usage. Physical therapies used as complementary methods improve mobility and quality of PD patients’ lives[11]. Complementary strategies to improve motor and balance coordination may help to reduce falls and disability from hip fractures [12,13].

Most of PD patients decrease their exercise to avoid falls ,especially in China , to avoid motor dilemma more patients hold Chinese traditional health maintenance prefer stay quietly, only few PD patients could do regular and helpful exercise[6]. So we design the research to describe the differences between the patients had regular CNMT and stayed quietly. And another destination of the present study was to assess CNMT therapy in PD treatment and to provide additional treatment options for PD patients.

2. METHOD

The present study was approved by the ethics committee of the local government and adhered to the tenets of the Declaration of Helsinki. Additionally, the written informed consent was obtained from patients and/or their family.

2.1 Patients

All PD patients diagnosed and kept stable drug dosage of dysmyotonia according to criteria of American Academy of Neurology ( AAN) were randomly divided into two groups without medication adjusted for one hole year[14], the treated group were given CNMT for 30 minutes every workday for one hole year. Clinical characteristics were tested when study began, the sixth month and the twelfth month and biochemical test results were recorded just before and after the study. All the results of treated group were compared with a control group without CNMT.

2.1.1

Inclusion Criteria

Participants were recruited from Jiangbin Hospital of China and supported by the government of Guangxi Zhuang Autonomous Region. Participants who lived near the hospital were at least 40 years of age, diagnosed according to the UK Brain Bank criteria at Hoehn and Yahr (H&Y) stages I–IV[15, 16] 。Participants could stand for 30 min and walk at least 6m with or without assistive device independently.

Exclusion Criteria

Participants were excluded when: (1).PD patients had medical problem such as serious complications or severe dementia, Fracture or trauma. (2) PD patients had evidence or history of neurological deficit such as cerebral stroke or neuromuscular disease. (3).The recruitments who happened sudden medical events dangerous for life and withdrawal by voluntary.

2.2 Types of interventions:

CNMT. (Coordination and Manipulation Technology therapy)

Coordination and Manipulation Technology (CNMT) therapy is consist of two parts, the one is coordination training originated in the breaststroke, the other part is manipulation therapy on spinal muscles. The coordination training is a method of imitation of breaststroke, which is called “Dry-land swimming”, a swimming action to imitate the posture of a swimming frog. Breaststroke training style as an excellent life-long sport is good for mental and physical health[17],especially after our adaption, it is suitable for the old people who cannot swimming. It is well known that breaststroke could improve the cardiovascular function, build strength endurance and muscle mass, and enhance the ability of flexibility and coordination. Another part of CNMT is the manipulation therapy on multifidus. It is reported that paraspinal muscle supplies strong power to control the stability of the spine and avoid abnormal gestures which is the most important factor lead to movement disorder[12, 18]. In the progression of PD paraspinal muscles become gradually degeneration especially multifidus. Physical therapies used as complementary methods improve mobility and quality of PD patients’ lives. In order to make more dyskinesia patients do exercise safely and improve their activities quickly, we proposed new easy training method called CNMT.

2.2.1 CNMT

CNMT therapy is a physical therapy composed of two parts, the one is coordination training(Co-T) which requests PD patients performed flat in the prone position relax themselves, then teach the patients imitate swimming as follows:

A. Before the exercise, thoracic extension, thoracic flexion and waist rotation Stretch are necessary. (3mins in total).

B. Prone on the mat with legs closed together straight, then raise the head or upper body slightly keep the mandibular border 10cm and both legs about 5cm distance vertical distance from the mat.

C. Then inhale while stretch arms and shoulder forward, at the same time bend knees and lift feet up to buttocks. Hold on for 3seconds with quiet breath.

D. Then exhale and keep raised head posture, arms begin slowly abduce to the shoulder level, bend the elbow and keep the small arms parallel to the trunk, stretch both arms forward with simultaneous turn feet out and push back with the bottom of the feet like a circle kick with the legs no contacting.

E. Rest for 5 seconds, and then turn to the original position as described above repeat.F. The training consists of 30min in total. Every patient tries to exercise twice. In the process

of this training, give 1minite rest every five minutes.

2.2.2 The manipulation therapy on paraspinal muscles of PD patients.

The manipulation therapy on multifidus of Parkinson’s disease patients is carried on after Co-T. The detail as follows:

A.  Massaging bilateral paraspinal muscles slightly with both the thumb or thenar eminence for 3 min.

B. After the exercise, thoracic extension (T6 to T12), thoracic flexion and waist rotation Stretch are necessary. (3min in total )

2.3 Types of outcome measures:

Assessments of participants were conducted at the same time interval respectively at the beginning of this study, the 6th month and the 12th month after the study began. Besides the Unified Parkinson’s Disease Rating Scale (UPDRS) (All four parts included). The Up and Go test (TUGT) were given then recorded the maximum step number (TUGT-SN) and time of process participants finished (TUGT –T). Balance was evaluated using the Berg Balance Scale (BBS) and balancing instrument (No.PRO-KIN254 made in TecnoBody, Italy). The path length and the track area of Center of gravity moving track were measured respectively when opening and closing eyes. All the results of participants’ biochemical tests performed using standard methods were recorded together with assessments.

3. Statistics

Patients recruitment were 39, 3patients of them were missed (1 in CNMT, 2 in Control group, 8.3%) the 1-year follow-up. Later over 20 patients’follow-up were carried forward. Continuous variables were examined for normality using the Kolmogorov-Smirnov test. In each group , every parameter’s differences( including three times assessments of UPDRS, OPL, OCA , C PL, CCA, TUGT-SN,TUGT –T and LVEF ) assessed during the time interval of 6 and 12 months were compared using the Repeated Measures analysis of General Linear Model, with the baseline of the first assessment. Between the groups the differences was

compared using the Wilcoxon rank sum test. Using the Greenhouse-Geisser for adjustment when p<0.05 in the sphericity assumption of the Mauchly test. Bonferroni test was applied to evaluate Relevant differences in time events. All statistics were performed by SPSS 20.0 and expressed as means and standard deviation. A 2-tailed P value less than 0.05 indicated statistical significance.

Table. 1: Clinical characteristics of patients

Items CNMT group Contrl group

N Mean± S.D N Mean±S.D

Men:Woman 18:04 7:07Yahn分级 3.05±0.84 2.64±0.84

II 7 8III 7 3IV 8 3

Age(year) 70.18±9.21 70.21±10.70

Height (cm) 163.61±6.84 162.50±5.85

Weight (kg) 58.60±7.485 59.93±7.54

BMI 21.97±2.18 22.65±2.24

SBP(mmHg) 127.82±9.79 127.86±9.58

DBP(mmHg) 74.55±6.79 74.07±7.03

HR(bp/min) 78.91±6.61 75.29±6.46

Pre-UPDRS-Part 1 15.86±9.88 13.07±8.46

Pre-UPDRS-Part 2 19.18±11.91 20.64±7.86

Pre-UPDRS-Part 3 22.20±7.80 23.32±6.70

Pre-UPDRS-Part 4 0.32±0.65 0.143±0.53

Pre-UPDRS-Total 57.23±29.06 57.18±21.56

Pre-BBS 42.45±10.112 43.36±5.84

Pre-OCA 718.50±321.80 1233.50±357.33

Pre-OPL 430.7±123.08 493.39±76.07

Pre-CCA 2166.55±1131.82 2617.3571±826.52

Pre-CPL 617.93±188.66 669.7143±55.52

Pre-LVEF (↑) 68.62±6.09 72.10±3.11

Pre-TUGT-SN 68.32±60.07 45.71±44.35

Pre-TUGT-T（s） 56.95±47.27 34.86±29.35

Values are means±S.D. Abbreviations: CI, confidence interval; UPDRS, Unified Parkinson Disease Rating Scale; BBS,Berg Balance score; OPL, Center of gravity moving track path length tested openning eyes; OCA ,Center of gravity moving track area tested openning eyes; C PL, Center of gravity moving track path length tested closing eyes; CCA, Center of gravity moving track area closing eyes area; TUGT-SN，Step

number of time up and go test; TUGT -T, Time of time up and go test ;UPDRS, OPL, OCA , C PL, CCA, TUGT-SN,TUGT -T, Pre-, before therapy.

Table 2:Baseline of Biochemical tests of patients

Items CNMT group Contrl groupN Mean± S.D N Mean± S.D

Pre-RBC(10e12/L) 4.33±0.705 4.38±0.60

Pre-Hb(g/L) 125.95±14.496 131.50±16.737

Pre-PLT(10e9/L) 174.14±43.17 200.14±39.03

Pre-HbA1a 1.5318±1.50 1.410±0.46

Pre- HbA1b 1.30±0.42 1.30±0.44

Pre-HbA1c 6.09±0.90 6.44±1.02

Pre-UG 1.05±.213 1.14±0.36

Pre-Uhb 1.00±0.00 1.07±0.27

Pre-UBLD1 1.45±2.46 6.07±12.16

Pre-Uwbc1 1 7.63±21.25 45.50±70.76

Pre-Uepi 0.09±0.29 0.57±1.34

Pre-Ubac1 5.41±12.50 10.29±4.83

Pre-U pyuria1 0.28±1.28 0.86±2.93

Valid N (listwise) 22 14

Abbreviations: red blood cell (RBC); platelet plug (PL); hemoglobin A (HbA); white blood cell(WBC);urine glucose ; epiphyte(epi); urine(U); before study (Pre-).

Table 3:Paired Samples test for Score changes before and after a whole year treatment

Subject CNMT group P-value Contrl group

P-value

TUGT-SN (↓) 11.18±17.52 0.011 -11.14±10.99

0.014

TUGT-T (s) (↓) 6.95±9.22 0.002 -6.21±7.95 0.011UPDRSA(↓) 2.23±3.12 0.009 -3±1.57 0.001UPDRSB(↓) 2.45±3.35 0.002 -4.07±4.16 0.006UPDRSC(↓) 2.66±3.12 0.007 -3.96±2.96 0.003UPDRST(↓) 7.61±6.63 0.001 -11.29±5.97 0.001BBS (↑) -3±3.89 0.006 3.71±3.45 0.003CCA (mm2) (↓) 238.64±251.8

70.001 -

322.86±214.19

0.001

CPL (mm) (↓) 60.28±96.54 0.026 -41.39±40.35

0.051

OCA (mm2) (↓) 172.45±175.4 0.001 -117.21±124.17

0.011

OPL (mm) (↓) 65.3±63.19 0.001 -45.83±60.96

0.015*

EF(LVEF,%) (↑) -4.61±5.33 0.003 2.02±4.16 0.182

A P value of <0.05 was considered significant.

Values are means±S.D. (↓) lower better; (↑) higher better.a Significant values.

Table 4: Compare the Difference of previous 6 month training results minus the following 6 month trainingresults

CNMT group Control group

D-value comparison

Mean±S. D t P Mean±S. D t P

UPDRS T -0.48±7.86 -0.285 0.778 -0.71±7.35 -0.363 0.722Berg -1.32±2.9 -2.131 0.045* 1.86±3.01 2.309

0.038*

OCA -54.73±210.86

-1.217 0.237 14.36±161.59

0.332 0.745

OPL -17.54±97.99

-0.84 0.411 28.46±45.05

2.363 0.034

CCA -47.55±335.74

-0.664 0.514 -16.71±295.61

-0.212 0.836

CPL -7.65±119.14

-0.301 0.766 20.75±31.61

2.456 0.029

EF -0.61±6.24 -0.458 0.652 0.68±3.88 0.654 0.524DT -0.59±11.83 -0.234 0.817 -0.5±4.83 -0.387 0.705UPDRSA -0.14±4.35 -0.147 0.884 -0.29±3.2 -0.334 0.743UPDRSB -0.41±2.5 -0.767 0.451 -0.93±4.71 -0.737 0.474UPDRSC 1.36±2.89 2.215 0.038* -2.04±2.77 -2.75 0.017

** P<0.05 was considered statistically significant.

Fig 5. Tendency Over Time as indicated by the real Clinical scales with antiparkinson drugs not changedSubject CNMT group CNMT group　 0M 6M 12M f η2 P-Value 0M 6M 12MBBS 42.68±10.22 44.6±9.50 45.68±9.97 10.15 0.41 0.005* 42.68±10.22 44.6±9.50 45.68±9.97CCA (mm2) 2123.55±1131.82 1980.45±1058.0

11884.91±1071.46 12.57 0.37 0.001* 2123.55±1131.8

21980.45±1058.01 1884.91±1071.46

CPL (mm) 617.91±188.66 583.95±145.80 557.63±165.24 5.7 0.006 0.214 617.91±188.66 583.95±145.80 557.63±165.24OCA (mm2) 718.50±321.78 604.91±323.42 546.05±316.87 14.84 0.41 0.001* 718.50±321.78 604.91±323.42 546.05±316.87OPL (mm) 430.17±123.08 388.75±134.35 364.86±128.29 13.36 0.39 0.001* 430.17±123.08 388.75±134.35 364.86±128.29TUGT-SN 68.31±60.68 62.81±56.71 57.14±52.98 8.07 0.278 0.008* 68.31±60.68 62.81±56.71 57.14±52.98TUGT-T (s) 56.95±47.27 53.18±45.69 41.07±33.16 8.1 0.278 0.001* 56.95±47.27 53.18±45.69 41.07±33.16UPDRSA 13.07±8.46 14.43±8.21 16.07±8.84 6.83 0.25 0.003* 13.07±8.46 14.43±8.21 16.07±8.84UPDRSB 20.64±7.86 22.21±6.96 24.71±8.16 10.06 0.324 0.002* 20.64±7.86 22.21±6.96 24.71±8.16UPDRSC 22.20±7.67 20.90±7.80 19.55±8.00 11.48 0.35 0.001* 22.20±7.67 20.90±7.80 19.55±8.00UPDRSD 0.32±0.65 0.18±0.39 0.05±0.21 4.47 0.18 0.031* 0.32±0.65 0.18±0.39 0.05±0.21UPDRST 57.57±28.68 53.52±27.86 49.85±27.44 19.8 0.49 0.001* 57.57±28.68 53.52±27.86 49.85±27.44EF(LVEF,%) 68.62±6.09 70.62±5.36 73.23±4.05 11.34 0.35 0.01* 68.62±6.09 70.62±5.36 73.23±4.05

* P<0.05 was considered statistically significant. Comparison of changes over time using repeated measurements analysis of variance plus a post hoc Bonferroni test relative to preoperative baseline.

Results

Overall clinical efficacy of CNMT therapy

In regard to age, UPDRS score, BBS score, parameters measured by balancing instrument and the other clinical outcomes, the two groups were not significantly different at the baseline (Table 1). After a whole year training, in all cases compared with pretherapy, notable scores changes conformed to patients in CNMT group showing greater improvement. As indicated, except for CPL, other parameters（CCA, OCA,OPL ） measured by balancing instrument showed significantly declined (P<0.01), which had the similar clinical implications as BBS increased (η2=0.41 , P<0.01 ). Results of TUGT and UPDRS diminished over a year. The total mean of LVEF was significantly climbed after NCMP therapy (p<0.001).

.

Clinical efficacy of Control group without regular exercise.

Comparing with the CNMT group , without regular exercise, the control group show the reversed result with longer time (TUGT-T), more step number (TUGT-SN) in TUGT and even higher score of UPDRS-III ,which revealed motor ability strikingly decreased over the time （ η2= （ 0.37,0.51 ） ， P<0.01 ） (Table2). The other subscales of UPDRS scores including total scores predominantly deteriorated which consistent in direction with patient’s clinical behavior. Balance ability was notable declined evidenced by Berg Balance scores (BBS) dramatically declined (p=0.003) and results of CCA, OCA and OPL enhanced (P<0.05). No statistical changes calculated from EF and CPL.

Balance Improvements in Motor Domains

After one year CNMT therapy without medicine doses altered, balance ability was significantly ameliorated. As indicated in table5, after a half year training BBS score increased statistically, a similar trend was observed for the next half year therapy(t=-2.131, P=0.045). On the contrary, in the control group BBS showed the even smaller over time (P<0.05) and OPL simulate BBS (P=0.034).All the other items’ score changes denoted of balance skill such as CCA, OCA and OPL did not show notable changes over a year.

Changes in biochemical tests

Unlike clinical scores, in the results of biochemical tests only platelet plug (PL) and urine red blood cells (UBLD) were notable different, with both PL and UBLD significantly declined within the normal reference rang after CNMT therapy, not the control group. No diverse effects were founded during and after the whole therapy in the CNMT group.

Trend of Degeneration

In control group, motor skill degenerated step by time. As is shown in the figure BBS score descending without regular training, which is also supported by increase of

CCA,OCA and OPL(P<0.05). Mental and psychiatric problem turned into even worse as indicated by the first part of UPDRS (η2=21.54,P<0.001).

DISCUSSION

The mobility of PD depends on many factors; however, because of subject heterogeneity it is difficult to compare the reported results directly. Physical therapy had been proved to facilitate efficacy of intervention, many research analyzed the reason physical therapy worked for transfer, posture, reaching and grasping, balance, gait, and physical capacity [12,13,19]. Nevertheless few simple and practical approach promoted avaiabale[19]. Thus, the present study was designed to gain further insight into the mobility of improvements in PD patients.

Published reported have described that swimming could improve coordination variability and stability of the body. Additionally, swimming could improve swimmer’s heart function by elevated ventricular ejection function [18,20,21]. Swimming as an aerobic exercise has been suggested to could positively improve motor action, balance, gait and quality of life by Meta analysis. But the important attention must to be paid is not all the patients could swimming or learn swimming, further more, it is extremely dangerous for PD patients to do sports or exercise in the water. For this reason, CNMT was devised to coordinated imitate the action of swimming on the ground ,therapy bed or other flat place, which is called “Dry-land Swimming” had been used for bodybuilding people and athletes by training both core muscle and coordination[22]. This Dry-land Swimming was once used for testing executive motor dysfunction in Parkinson Disease, but never used for long term training. In this study, after swimming action finished, PD patients could accept manual therapy on peripheral spinal muscles to alleviate the tired perception. As was reported, paraspinal muscle of PD patients become gradually degeneration, which directly lead to abnormal gesture and increasing occurrence of fall[3]. Paraspinal muscle especially Multifidus has been evidenced to supply effectively strong power to control the stability of the spine. Therefore we design the study to investigate the efficiency of the combination of Dry-land Swimming training and paraspinal manipulation. As all results shows that participants in CNMT expressed their conforming of physical performance improvement and joy on the participating. This study is the first study to utilize new Dry-land Swimming training for training in PD patients. Additionally, as data supported, physical performance is significantly improved.

As a relatively large-scale and long term study for PD, this retrospective cohort study reported the general results from a single institution in Asia. As were demonstrated in the previous reports, the current study demonstrated a new easier and more effective physical therapy for PD. PD patients participated in the CNMT group got sustained benefits after one year clinical training. The results indicated motor skill improved and balance deficient alleviated. After CNMT therapy, PD patients spent fewer time (average 6.95s) and fewer step (average, 11.18) in UPGT test. Parameters originated from balance instrument show notably increased, which correspond to BBS. In current study, we get conclusion that, compared to test in closing eyes, balance ability improve more effectively in opening eyes test over the time (η2=0.41,P<0.001).

However ， instead of improvement, motor and balance dysfunction deteriorated in control group. In accordance with previous reports, the current study proves deteriorated features of all Parkinson patients without exercise in daily life [23,24]. The results support that fixed exercise program is related to the progression of PD[25].

Though all patients did not have serious cardiac function defection before this study, CNMT group showed significantly elevated in LVEF (t=5.945, P<0.01). Precise pathophysiology of LVEF improvement is not clearly understood. However, as reported in the previous researches the pathophysiological mechanism properly responsible for two reasons. The one is that dry-land swimming as an aerobic exercise were carried out companied by breathing control, which has been successfully confirmed as effective way to evaluate cardiovascular function in heart disease patients[9, 26-28]. In the control group, we did not get the positive or negative result on cardiovascular function due to short time observation.

In this study mental and psychiatric problems were also improved with the time duration in CNMT group, which revealed in the first subscale of UPDRS(η2=0.25,P=0.003). Published articles suggested aerobic exercise could improves mood of mild to moderate PD[29]. However, it is still in controversial on the relationship between psychology and exercise. Cruise KE reported that no significant effect were demonstrated for mood [30]. Only possible factors we speculate on the explaining is exercise seemed to be considered that exercise partially reverses degeneration on hippocampal proteins [31].

This current study indicated that without exercise PD in control group had a higher blood cell occurrence (t=-3.25, P=0.004), not in the CNMT group. The detail causes might be explained as: exercise could improve renal function by elevating high density lipoprotein or experience a decrease in cystatin C-estimated GFR [32,33].

Several limitations involved in this study, such as small size of sample and short training duration. Meanwhile, as a pilot study our results need to be confirmed in further larger trails. The detailed mechanism of improvement of mobility, balance skill and heart function after CNMT had not been described nor demonstrated in this pilot study. More often, however, subsequent research would discuss further due to larger scale and longer time.Finally, in this study we did not set another group to compare the effectiveness and utility of different sport or physical therapy such as Chinese traditional exercise Tai Chi or classical sport swimming.

Despite this pilot study has been limited by relatively small size of sample and short training duration, the results support that CNMT may be safe and effective for PD with Yahr stage II to IV. CNMT could be widely used for family or community therapy for PD patients, and could be a self training Strategy either.

Acknowledgements.

We would like to express our thanks to Caiyou Hu (Department of Neurology, Jiangbin hospital, Guangxi Zhuang Autonomous Region) for his assistance with this project. We would like to acknowledge Shengli An (Department of Biostatistics, School of Public Health and Tropical medicine, Southern Medical University) for assistance with statistics support.

Reference .

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