Therapeutic value of exercise training in Parkinson’s... : Medicine & Science in Sports & Exercise (2024)

Parkinson’s disease (PD) is characterized by three main features tremor, akinesia, and rigidity. The clinical manifestation differs between akinetic-rigid, tremor-dominant, and akinetic-rigid-tremor type. The course of the disease varies clearly between individual patients. Slow progression is seen in elderly patients, usually with tremor-dominant clinical manifestation, rapid progression is more often reported in young patients and in akinetic-rigid clinical manifestation. Because the introduction of L-dopa in medical treatment of PD, mortality and severe morbidity have decreased. Besides medication, physiotherapy is an established treatment of movement disorders. There is a general consensus that physiotherapy is likely to improve the motor condition and physical state of patients with PD, especially in advanced stages of the illness. The aim of physiotherapy in advanced stages of PD is to prevent joint contractures in bed-ridden patients.

However, there are only a few studies reported on the effects of sports activity in slightly to moderately disabled parkinsonian patients. In 1992, Kuroda et al. (¹²) reported an investigation of 438 parkinsonian patients over a follow-up period averaging 4.1 yr. The aim of the study was to investigate the influence of physical activity on the mortality in parkinsonian patients. Patients who were exercising exhibited the lowest mortality. The results of this study suggest that physical exercise in daily life seems to lower mortality in PD. Hence, physical activity is one factor influencing survival rate in PD, but a bias by patient’s selection cannot be completely excluded. A study conducted by Sasco et al. (¹⁹) showed a slight protective effect of physical exercise on the risk of developing PD. On the other hand, a striking reduction in physical activity is found during the course of PD (⁶).

The benefit of intensive exercise training on motor disability in PD is discussed controversially. Comella et al. (⁴) found a significant improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS) part 2 (activities of daily living) and UPDRS part 3 (motor scores) after intensive physical training over 4 wk in a randomized single-blind cross-over study evaluating physical disability in medium staged parkinsonian patients. In Comella’s study the improvement returned to baseline after 6 months without specific training. Formisano et al. (⁷) found an improvement of motor disability in PD by an intensive physical therapy program including passive and active mobilization exercises lasting over 4 months. Palmer et al. (¹⁶) compared the effects of karate training with a special stretching program of the United Parkinson Foundation. After a training period of 12 wk, the outcomes in both groups were similar. Functional improvement was observed in gait, arm tremor, and coordination but not in active movements involving both arms and trunk. In contrast to these results, Gibberd et al. (⁸) reported no improvement by exercise training. He compared physiotherapy, including proprioceptive neuromuscular facilitation, and Bobath and Peto’s methods with occupational therapy. There was no statistical difference between both groups and no significant improvement in both groups.

The objective of our study was first to investigate the improvement of motor disability, mood, and subjective well-being by an intensive motor training program that was focused on sports activities and, second, evaluation of potential long term effects of such motor training.

METHODS

General design.

The study was designed as an open long-term trial over 20 wk. All medication was kept stable during the study period. Patients who were absent from exercise training more than two times were excluded. Standardized ratings were performed before starting the study (examination 1), after 7 wk of systematic training (examination 2), and at endpoint of the training period after 14 wk (examination 3). To evaluate potential long-term efficacy, a follow-up rating 6 wk after termination of the training program was performed (examination 4). All patients were outpatients and the training program was designed as outpatient exercise training rather than remedial gymnastics.

Patient characteristic.

Sixteen patients with idiopathic PD (UK-PDSBB criteria;¹¹) were included in the study. Exclusion criteria were any concomitant neurological disease as well as severe heart or lung disease. Patients who were not able to walk and stand without help due to PD-specific disability were also excluded because intensive physical training requires a hom*ogenous group of patients capable to perform the complete training program. Before the start of the training program, a careful general physical examination was performed in all patients, including an ECG to screen for cardiovascular risk assessment. Table 1 shows the main demographic data of the patients. All patients gave written consent to participate in the study and the study was approved by the ethical committee of the University Frankfurt.

Training program.

Intensive regular exercise training consisting of various standardized sports activities was performed twice weekly over 14 wk. Each training unit lasted 1 h. The rationale of treatment in PD is uncertain. There is still considerable debate about the pathophysiology of movement impairment in PD (^14,15); therefore, it is difficult to develop a training program specific for motor disability improvement in PD. There are symptoms directly related to PD, functional problems that are due to the ageing process and additionally factors secondary to the disease like muscle atrophy caused by impaired movements (¹⁰). Analysis of parkinsonian gait (¹³) has shown that reduced speed of forward progression in parkinsonian patients is due to diminished stride length in combination with increased cycle duration. The time of the double-limb supported phase of gait is increased. Flexion of hip joint as well as flexion and extension of knee joint are reduced. The excursion in the ankle is reduced. There is diminished or lacking transverse rotation of the pelvis during walking. Patients move with a constant speed and are mostly unable to increase velocity of movements quickly (¹⁰). According to these studies and the known phenomena, slowness of movements, weakness, rigidity, and postural impairment, the training program was focused to improve these impairments in PD. The content of exercise training is listed in Table 2 A and 2B. The validity of the exercises we carried out was tested in a healthy subjects.

Once per week the training took place in warm water to increase muscle strength against the water resistance and to reduce trunk stiffness and rigidity. The second training program of the week was held in the gymnasium to improve initiation of movements, gait, flexibility, and coordination of motor skills. In the gymnasium music was used as an external stimulus to initiate movements, because it is known that in the basal ganglia different pathways are involved in externally and internally cued movements. (^5,17). Circuits of externally cued movements are less disturbed in PD. Additionally, improved performance of movements may be due to increased attention of patients in anticipation of the external cue (¹). Therefore, external stimuli were used for initiation and continuation of movements.

Data acquisition.

The complete test battery included rating scales for PD-specific motor disability, sport-specific motor disability, and psychometric data. PD-specific motor disability was rated by the Unified Parkinson’s Disease Rating Scale (UPDRS), including measurement of cognitive function (subscore 1), activity of daily living (subscore 2), motor scores (subscore 3), complications of treatment (subscore 4), modified stage rating according to Hoehn and Yahr (subscore 5), rating of independence in daily living (subscore 6), and by the Columbia University Rating Scale, focused on measuring motor scores. For detailed evaluation UPDRS, subscore 4 was divided into three subgroups—fluctuations, dyskinesias, and dystonias. Additionally, modified Webster Step Second Test (2 × 10 m walking with two 180° turns) and Purdue Pegboard (sticking of 20 pins with each hand as fast as possible) were performed in all patients. The sport-specific Basic Motor Test (BMT) includes subscores measuring strength, flexibility, and coordination of motor skills (performing of two different movements simultaneously, e.g., balancing on a line and bouncing a ball). Psychometric data were registered by Mini Mental Status (MMS) for dementia, Adjective Mood Questionnaire of Zeersen, and Sickness Impact Profile (SIP) with SIP subscores (SD1 physical score and SD2 psychosocial score) for subjective well-being. The complete test battery was performed in all patients.

Statistical analysis was done by MANOVA, multiple analysis of variances in a one-factor design representing repeated measurement variables.

RESULTS

All patients completed the study. There were no medical problems during the training period related to the exercise program.

Influence of sports activities on motor disability.

There was a clear improvement in the UPDRS Σ score (P < 0.0001) and CURS Σ score (P < 0.0001) (Fig. 1). Most subscores of UPDRS also declined significantly: UPDRS part 1 (cognitive function and mood, P < 0.0001), part 2 (activities of daily living, P < 0.004), part 3 (motor score, P < 0.0001), part 4 (complications of treatment, P < 0.001), and part 6 (modified rating of activity of daily living according to Schwab/England, P < 0.007) (Fig. 2). UPDRS part 4 scoring complications of treatment in PD is divided in three parts: fluctuations, dyskinesias, and dystonia. There was no influence on fluctuations and dystonia by exercise training but there was on duration and severeness of dyskinesias. Dyskinesias improved in seven of the eight patients with dyskinesias. The exercise program had no effect on dyskinesias in one patient. In five patients, duration and severeness of dyskinesias improved, in one patient only duration of dyskinesias decreased, and in one patient severity of dyskinesias declined. Apart from the long-term effect, there was also a short-term effect on involuntary movements: immediately after each training session, patients with dyskinesias reported an improvement of dyskinesias during the exercise training. Subscore 5 (modified stage rating according to H&Y) did not change during physical therapy.

Walking time for Webster Step Second Test decreased significantly (P < 0.0001) during the training period (Fig. 2). Time for Purdue-Pegboard 20 pin improved on the right (P < 0.0001) and left (P < 0.004) hand significantly (Fig. 3).

BMT Σ score showed clearly significant improvement (P < 0.0001). The subscores of BMT to strength (P < 0.0001), motor skill coordination (P < 0.0001), and flexibility (P < 0.0001) also improved significantly. Data of BMT Σ score and BMT subscores are shown in Figure 4.

Influence of sports activities on subjective well-being and cognitive function.

There was a clear improvement of subjective well-being. Σ scores of Adjective Mood Questionnaire of Zeersen improved significantly (P < 0.0001). In addition Σ score of Sickness Impact Profile showed significant improvement (P < 0.002) as well as the SIP subscores to physical (SD1, P < 0.001) and psychosocial (SD2, P < 0.006) dimension (Fig. 5). Cognitive function measured by Mini Mental State remained unchanged during the study, exam._1–4: mean ± SD: 28.7 ± 1.8 → 28.7 ± 1.7 → 28.6 ± 2.0 → 28.8 ± 1.9 points (NS).

Long-term effects.

There was only a minimal loss of regained motor skills 6 wk after termination of intensive exercise therapy focused on sports activity. A sustained ongoing effect outlasting the active training period for at least 6 wk could be achieved.

DISCUSSION

The results of our study show a statistically significant improvement of PD-specific motor disability and of sport-specific motor disability. The UPDRS Σ score and CURS Σ score as well as most UPDRS subscores and BMT Σ score improved during exercise therapy focused on sports activities. We found a clear improvement of all motor scores by using a varied athletic training including resistance exercises in water to increase strength as well as exercises increasing flexibility and balance (Pezzi ball, roll exercises, and stance on one leg). We found a clear improvement of all motor scores. The decrease in walking time shown in the Webster Second Step Test confirmed the necessity to practice gait exercises as well as gait preparation exercises like active hip, knee, and ankle movements. The improvement of gait in PD by an exercise program as performed in our study confirmed earlier results showing that the sequences of complex movements characteristic of normal gait are not primarily disrupted (¹⁸), the changes being merely of quantitative nature with more or less pronounced decreases in range or speed of movements (¹³). Modified Hoehn and Yahr stage rating did not differ significantly before and after the study. This may be due to large steps between Hoehn and Yahr staging; the rating scale is somewhat insensitive to minor changes in PD. During the training subjective well-being also increased in both questionnaires (AMQZ and SIP). Cognitive function was kept stable during the training period. There seemed to be a contradiction between results of MMS and subscore 1 in UPDRS, but subscore 1 of UPRDS includes questions concerning mood. The improvement of subscore 1 was caused by improvement of mood.

Due to different study designs, especially due to different training methods, the results of our study are difficult to compare with former studies. For reasons of study design, our study is best compared with Formisano’s study (⁷). Formisano et al. (⁷) found beneficial effects of physical therapy including an active and passive mobilization program in parkinsonian patients. We can confirm improvement of motor disability by exercise training. Palmer et al. (¹⁶) also found an improvement of general motor disability in PD by exercise therapy. However, in Palmer’s study, there was no difference in the outcome between karate training and a stretching program. These authors, however, also observed worsening of complex arm-trunk movements, which was suspected to be the consequence of increased stiffness after the exhausting exercise program and a limiting factor of exercise programs in PD. The authors, however, did not find any change in muscle rigidity in their patients. Therefore, their conclusion seems to be controversial as to their own results. In contrast to Palmer’s observation (¹⁶), complex arm-trunk movements are improved in our study. These data are shown in BMT subscore coordination of motor skills (Fig. 3). There is a significant improvement of complex motor sequences. In none of the other studies were motor rating scales for measuring non-PD-specific motor disability used. Because of our study design using a sport-specific motor rating scale besides PD-specific rating scales, we were able to get more detailed information about pure motor improvement in simple and complex motor sequences. There is less psychological influence on the test results of BMT.

Improvement of dyskinesias by exercise training was unexpected but seen in our study. This phenomenon corre-sponds well with clinical reports on an improvement of dyskinesias after physical activities in individual patients. Improvement of dyskinesias are reported as short-term effect immediately after a training session (subjective reports by patients; no systematic data) and during the whole training period (UPDRS subscore 4). Improvement of dyskinesias comprises severity and duration of dyskinesias. There is no positive influence on dystonia, only on involuntary movements. The pathomechanism of this phenomenon remains unclear. Chaouloff (³) found an increase of dopamine release and turnover in rats during exercise and a decreased dopamine turnover after exercise due to a D₂-receptor hypersensitivity in rats. L-dopa pharmaco*kinetics might also be modified by exercise. Absorption of L-dopa during exercise was studied by Carter et al. (²) in 10 parkinsonian patients. She found delayed L-dopa absorption in five, increased in three, and remained unaffected L-dopa absorption in two patients during exercise. In contrast to these results, Goetz et al. (⁹) did not find any influence of exercise on L-dopa concentration in plasma but in his study exercise started only 1 h after L-dopa administration. According to the pharmaco*kinetics of L-dopa, peak concentrations of L-dopa are reached 30–45 min after administration. Reduction of peak dosis dyskinesias in our study suggests that according to Carter et al. (²) L-dopa absorption might be modified during exercise.

There seems to be a long-term benefit of exercise therapy outlasting the active physical training for at least 6 wk, but we have no data about the duration of this long-term effect. Our patients refused being without sports activity longer than 6 wk. Comella et al. (⁴) described a return to baseline of physical fitness rated by UPDRS subscores 6 months after physical rehabilitation. Due to general developing of muscle atrophy and functional decline after immobilization, it is to be considered that a deterioration of physical fitness will be exhibited about 6–8 wk after termination of exercise training.

Our study was designed as an open trial and improvement was found for subjective well-being as well as for motor performance. A bias might be caused by the fact that better general care and more intensive attention was paid to the patients during the study and they got a positive social experience. This might be at least partially responsible for the improvement of subjective well-being. Interactions between subjective well-being and motor performance cannot be completely excluded. There are two interfering problems: first, exercise training improves well-being in most patients, and second, improved well-being can lead to better motor performance. But the striking improvement of the basic motor test points out that there is a real motor improvement, because BMT Σ score measures only motor performance. Unlike UPDRS, it includes no self-rating and no rating of mood.

Thus, in agreement with a number of previous studies, the results of our investigation suggest a benefit of exercise therapy in PD. But in contrast to these studies, we performed a special program focused on sports activities, which might be useful especially in mild to moderate stages of the disease and can be performed in groups and in outpatients. We conclude that physical therapy is helpful in PD and can improve both PD-specific and sport-specific motor disability. The training program used in our study is based on pathophysiological considerations and results of earlier studies, but there is still a lack of validity of exercise training in PD. Therefore, further work is needed to develop more specific physiotherapeutic programs tailored to different stages of PD.

This study received a grant from the Deutsche Parkinson Vereinigung.

REFERENCES