Patients with Parkinson's disease (PD) lead a sedentary lifestyle, unable or unwilling to adhere to traditional motor activity programmes, due to physical and mental limitations. Yet the effects of physical exercise to improve motor and non-motor symptoms and slow the progression of the disease are universally known: from the reduction of selective neurodegeneration of dopaminergic neurons to the adaptive neuroplasticity conferred by movement, from structural modifications such as neurogenesis or synaptogenesis to reduction of oxidative stress and release of neurothrophic factors. Finally, exercise promotes a better absorption of the levodopa always present in the therapy of Parkinson's patients. Therefore, it is needed to find a training methodology for them that provides an immediate feeling of well-being that gives them motivation and perseverance, with a convenient ratio between spent time and exercise efficacy. This is the first study evaluating the application of electromyostimulation training (WB-EMS) on subjects with Parkinson's disease. For this reason, this project was organised in two studies, an acute pilot study and a chronic study. The aim of the pilot study was to evaluate the patients’ reaction to this new training methodology and to find the most suitable and safe type of stimulation for these subjects. A training protocol proposed by the company Miha Bodytec was admnistered. Ten subjects (age 72.60 6.82) were recruited for the acute study and underwent 20 min of physical activity with the superimposition of WB-EMS (WB-EMS) and, after four weeks, performed the same protocol without WB-EMS (no WB-EMS). Electromyostimulation was administered by intermittent stimulation, with 4 s WB-EMS/4 s rest, at 85 Hz, 350 µs. During the stimulation, patients were asked to perform a maximal isometric contraction. A fitness assessment and blood sample collection was performed to assess the levels of neurotrophic factors (BDNF, FGF21, proNGF, mNGF); samples were collected before, after 15min and 60min to end of the intervention. The RM-ANOVA showed significant improvements in sit to stand (p < 0.01), arm curl (p < 0.01), handgrip (p < 0.01) and soda pop test (p < 0.01) after WB-EMS intervention. Higher serum levels of proNFG were observed in the WB-EMS condition compared to no WB-EMS after 60 min post-intervention (p= 0.0163). The effect of WB-EMS confirmed the ability of electrostimulation to modulate the amount of proNGF. The positive impact of the WB-EMS protocol on physical functioning, and oculo-manual coordination, makes this intervention a promising strategy to improve motor and non-motor symptoms in PD patients. This study showed that neurotrophic factors, strongly correlated with cognitive improvement and walking ability, were not particularly stimulated. For this reason, we have decided to introduce another training protocol for the next phase of our study: the aerobic trainig. The aim of the chronic study was to find the most suitable and effective training methodology for this population. Twenty-five subjects (age 72.08 ± 6.07) were recruited for this study. They were randomly assigned to three groups: Strength Training Group (STG) (age 72.37 ± 7.40), Endurance Training Group (ETG) (age 72.89 ± 2.76) and Control Group (CON) (age 70.87 ± 7.77). The STG group performed the training as in the acute study (duration 20min, intermittent stimulation, with 4 s WB-EMS/4 s rest, at 85 Hz, 350 µs). The progression of the training was programmed every 3 weeks. The ETG group underwent 20 min of aerobic training on a remergometer combined with a superimposed and supervised WB-EMS stimulus using the metabolic protocol (rectangular stimulation at 7 Hz, 350 μs, continuous pulse duration). The progression of the training was programmed on the basis of the heart rate reserve (HRR) starting at 60% HRR in the first week, increasing the intensity by 5% every 3 weeks, up to 80%HRR in 12th week. The CON group did not carry out any kind of training. Before and at the end of the trial, physical fitness and cognitive performances were assessed and blood samples were collected to assess the levels of neurotrophic factors (BDNF, FGF21) and α-synuclein levels. The RM-ANOVA showed significant improvements in both ETG and STG groups in arm curl (both ps= 0.003) and sit to stand (p= 0.004 and p= 0.030 respectively). In addition, the ETG group was able to cover a greater distance in the 6-minute walk test than the pre-intervention (p< 0.001) and than STG group (p= 0.004). The same result emerged for the Tinetti balance and gait test, where the ETG group showed higher balance and walking ability than the pre-intervention (p< 0.001) and than STG group (p= 0.002). With regard to cognitive performance, results showed an improvement in general cognitive function (MMSE) both in the ETG group (p= 0.002) and in the STG group (p= 0.010). Another important result concerns the perception of fatigue (PFS-16), where the ETG group reported a lower fatigue than ETG (p= 0.013) and CON (p< 0.001) groups; in addition, the CON group reported a higher perception of fatigue than pre-intervention (p= 0.032). Lower serum levels of α-synuclein were observed after ETG training (p= 0.037). In contrast, higher serum levels of FGF-21 were observed after ETG training (p= 0.023). WB-EMS training is an effective and well-tolerated training strategy for Parkinson's patients. Endurance training combined with WB-EMS was more effective than strength training in improving physical fitness, cognitive performances and the level of neutrophic factors, which is correlated with an improvement in global cognitive function and severity of Parkinson's disease. The FGF plays a crucial role in the survival of neurons as well as in neuroinflammation and mitochondrial dysfunctions caused by abnormal aggregation of α-synuclein. FGF21 infact reduces the accumulation of alpha synnuclein, reducing its toxicity. Moreover, this endocrine hormone easily crosses the blood-brain barrier by simple diffusion, increasing its protection factor.
I pazienti con malattia di Parkinson (PD) conducono uno stile di vita sedentario, non potendo o non volendo aderire a programmi di attività motoria tradizionali, a causa di limitazioni fisiche e mentali. Eppure gli effetti dell'esercizio fisico per migliorare i sintomi motori e non motori, e rallentare la progressione della malattia sono universalmente noti: dalla riduzione della neurodegenerazione selettiva dei neuroni dopaminergici alla neuroplasticità adattativa conferita dal movimento, da modifiche strutturali come la neurogenesi o la sinaptogenesi alla riduzione dello stress ossidativo e al rilascio di fattori neurotrofici. Infine, l'esercizio favorisce un migliore assorbimento della levodopa sempre presente nella terapia dei pazienti di Parkinson. Pertanto, è necessario trovare una metodologia di allenamento per loro che induca una sensazione immediata di benessere e che dia loro motivazione e perseveranza, con un rapporto conveniente tra tempo di allenamento ed efficacia dell'esercizio. Questo è il primo studio che valuta l’applicazione di un allenamento con elettromiostimolazione (WB-EMS) su soggetti affetti da Parkinson. Per questo motivo il presente progetto è stato organizzato in due lavori, uno studio pilota in acuto e uno studio in cronico. Lo studio pilota ha avuto lo scopo di valutare la reazione dei soggetti a questa nuova metodica di allenamento e di trovare la tipologia di stimolazione più adatta e sicura per questi soggetti. È stato utilizzato un protocollo di allenamento già proposto dall’azienda Miha Bodytec. Dieci soggetti (età 72,60 6,82) sono stati reclutati per lo studio in acuto e sono stati sottoposti a 20 min di attività fisica con la superimposizione delle WB-EMS (WB-EMS) e, dopo quattro settimane, hanno eseguito lo stesso protocollo senza WB-EMS (no WB-EMS). L’elettromiostimolazione è stato somministrata con una stimolazione intermittente, con 4 s WB-EMS/4 s riposo, a 85 Hz, 350 µs. Durante la fase on della stimolazione è stato chiesto ai pazienti di effettuare una contrazione massimale isometrica. È stata effettuata una valutazione della forma fisica e una raccolta di campioni di sangue, per valutare i livelli di fattori neurotrofici (BDNF, FGF21, proNGF, mNGF); i prelievi sono stati raccolti prima, dopo 15min e dopo 60min dal termine dell'intervento. L'RM-ANOVA ha mostrato miglioramenti significativi nel sit-to-stand (p < 0,01), arm curl (p < 0,01), handgrip (p < 0,01) e soda pop test (p < 0,01) dopo l'intervento con WB-EMS. Livelli sierici più alti di proNFG sono stati osservati nella condizione WB-EMS rispetto al no WB-EMS dopo 60 min post-intervento (p = 0.0163). L'effetto della WB-EMS ha confermato la capacità dell'elettrostimolazione di modulare la quantità di proNGF. L'impatto positivo del protocollo WB-EMS sul funzionamento fisico, e la coordinazione oculo-manuale, rende questo intervento una strategia promettente per migliorare i sintomi motori e non-motori nei pazienti PD. Questo studio ha dimostrato che i fattori neurotrofici, fortemente correlati con il miglioramento cognitivo e la capacità di camminare, non erano particolarmente stimolati. Per questo motivo, abbiamo deciso di introdurre un altro protocollo di allenamento per la prossima fase del nostro studio: l’allenamento aerobico. Lo studio in cronico ha avuto lo scopo di ricercare la metodica di allenamento più adatta ed efficace per questo target di popolazione. Venticinque soggetti (età 72.08 ± 6.07) sono stati reclutati per questo studio. Sono stati assegnati in modo casuale in tre gruppi: Strength Training Group (STG) (età 72,37 ± 7,40), Endurance Training Group (ETG) (età 72,89 ± 2,76) e gruppo di Controllo (CON) (età 70,87 ± 7,77). Il gruppo STG ha eseguito lo stesso allenamento che è stato effettuato nello studio in acuto (durata 20min, stimolazione intermittente, con 4 s WB-EMS/4 s riposo, a 85 Hz, 350 µs). La progressione dell'allenamento è stata programmata ogni 3 settimane. Il gruppo ETG è stato sottoposto a 20 minuti di allenamento aerobico su remoergometro combinata ad uno stimolo WB-EMS superimposto e supervisionato utilizzando il protocollo metabolico (stimolazione rettangolare a 7 Hz, 350 μs, durata dell'impulso continua). L'intensità di questa tipologia di allenamento è stata programmata sulla base della frequenza cardiaca di riserva (HRR) iniziando dal 60%HRR nella prima settimana, incrementando l’intensità del 5% ogni 3 settimane, fino ad arrivare all’80%HRR nella 12 settimana. Il gruppo CON non è stato sottoposto ad alcuna tipologia di allenamento. Prima e al termine della sperimentazione, è stata effettuata una valutazione della forma fisica, delle performance cognitive e una raccolta di campioni di sangue, per valutare i livelli di fattori neurotrofici (BDNF, FGF21) e i livelli di α-sinucleina. L'RM-ANOVA ha mostrato miglioramenti significativi sia nel gruppo ETG che STG nell’arm curl (entrambe le p= 0.003) e nel sit to stand (p= 0.004 e p= 0.030 rispettivamente). In aggiunta, il gruppo ETG è stato in grado di coprire una maggiore distanza nel test del cammino di 6 minuti rispetto al pre intervento (p< 0.001) e al gruppo STG (p= 0.004). Lo stesso risultato è emerso per il test di equilibrio e andatura di Tinetti, dove il gruppo ETG ha mostrato maggiore equilibrio e capacità di cammino rispetto al pre intervento (p< 0.001) e al gruppo STG (p= 0.002). Per quanto riguarda le performance cognitivi, i risultati evidenziano un miglioramento della funzionalità cognitiva generale (MMSE) sia nel gruppo ETG (p= 0.002) che nel gruppo STG (p= 0.010). Un altro risultato importante riguarda la percezione della fatica (PFS-16), dove il gruppo ETG ha riportato un minor senso di fatica rispetto al gruppo ETG (p= 0.013) e CON (p< 0.001); inoltre, il gruppo CON ha riportato una maggiore percezione della fatica rispetto al pre intervento (p= 0.032). Livelli sierici più bassi di α-sinucleina sono stati osservati dopo l’allenamento ETG (p= 0.037). Al contrario, livelli sierici più alti di FGF-21 sono stati osservati dopo l’allenamento ETG (p= 0.023). L’allenamento con WB-EMS è risultata una strategia di allenamento efficace e ben tollerata dai soggetti affetti da Parkinson. L’allenamento aerobico con la superimposizione di WB-EMS è risulato essere più efficace dell’allenamento di forza nel migliorare la forma fisica, le performance cognitive e il livello di fattori neutrofici, correlati ad un miglioramento della funzionalità cognitiva globale e alla severità della patologia del Parkinson. L'FGF gioca un ruolo cruciale nella sopravvivenza dei neuroni così come nella neuroinfiammazione e nelle disfunzioni mitocondriali causate dall'aggregazione anomala di α-sinucleina. L’FGF-21 riduce infatti l'accumulo di α-sinucleina, riducendo la sua tossicità. Inoltre, questo ormone endocrino attraversa facilmente la barriera emato-encefalica per semplice diffusione, aumentando il suo fattore di protezione.
Effetti in acuto ed in cronico di protocolli di attività fisica con l'applicazione dell'elettromiostimolazione whole body sulle prestazioni fisiche, cognitive e sulle variazioni dei fattori di crescita in soggetti affetti da Parkinson
BUONSENSO, Andrea
2022-10-04
Abstract
Patients with Parkinson's disease (PD) lead a sedentary lifestyle, unable or unwilling to adhere to traditional motor activity programmes, due to physical and mental limitations. Yet the effects of physical exercise to improve motor and non-motor symptoms and slow the progression of the disease are universally known: from the reduction of selective neurodegeneration of dopaminergic neurons to the adaptive neuroplasticity conferred by movement, from structural modifications such as neurogenesis or synaptogenesis to reduction of oxidative stress and release of neurothrophic factors. Finally, exercise promotes a better absorption of the levodopa always present in the therapy of Parkinson's patients. Therefore, it is needed to find a training methodology for them that provides an immediate feeling of well-being that gives them motivation and perseverance, with a convenient ratio between spent time and exercise efficacy. This is the first study evaluating the application of electromyostimulation training (WB-EMS) on subjects with Parkinson's disease. For this reason, this project was organised in two studies, an acute pilot study and a chronic study. The aim of the pilot study was to evaluate the patients’ reaction to this new training methodology and to find the most suitable and safe type of stimulation for these subjects. A training protocol proposed by the company Miha Bodytec was admnistered. Ten subjects (age 72.60 6.82) were recruited for the acute study and underwent 20 min of physical activity with the superimposition of WB-EMS (WB-EMS) and, after four weeks, performed the same protocol without WB-EMS (no WB-EMS). Electromyostimulation was administered by intermittent stimulation, with 4 s WB-EMS/4 s rest, at 85 Hz, 350 µs. During the stimulation, patients were asked to perform a maximal isometric contraction. A fitness assessment and blood sample collection was performed to assess the levels of neurotrophic factors (BDNF, FGF21, proNGF, mNGF); samples were collected before, after 15min and 60min to end of the intervention. The RM-ANOVA showed significant improvements in sit to stand (p < 0.01), arm curl (p < 0.01), handgrip (p < 0.01) and soda pop test (p < 0.01) after WB-EMS intervention. Higher serum levels of proNFG were observed in the WB-EMS condition compared to no WB-EMS after 60 min post-intervention (p= 0.0163). The effect of WB-EMS confirmed the ability of electrostimulation to modulate the amount of proNGF. The positive impact of the WB-EMS protocol on physical functioning, and oculo-manual coordination, makes this intervention a promising strategy to improve motor and non-motor symptoms in PD patients. This study showed that neurotrophic factors, strongly correlated with cognitive improvement and walking ability, were not particularly stimulated. For this reason, we have decided to introduce another training protocol for the next phase of our study: the aerobic trainig. The aim of the chronic study was to find the most suitable and effective training methodology for this population. Twenty-five subjects (age 72.08 ± 6.07) were recruited for this study. They were randomly assigned to three groups: Strength Training Group (STG) (age 72.37 ± 7.40), Endurance Training Group (ETG) (age 72.89 ± 2.76) and Control Group (CON) (age 70.87 ± 7.77). The STG group performed the training as in the acute study (duration 20min, intermittent stimulation, with 4 s WB-EMS/4 s rest, at 85 Hz, 350 µs). The progression of the training was programmed every 3 weeks. The ETG group underwent 20 min of aerobic training on a remergometer combined with a superimposed and supervised WB-EMS stimulus using the metabolic protocol (rectangular stimulation at 7 Hz, 350 μs, continuous pulse duration). The progression of the training was programmed on the basis of the heart rate reserve (HRR) starting at 60% HRR in the first week, increasing the intensity by 5% every 3 weeks, up to 80%HRR in 12th week. The CON group did not carry out any kind of training. Before and at the end of the trial, physical fitness and cognitive performances were assessed and blood samples were collected to assess the levels of neurotrophic factors (BDNF, FGF21) and α-synuclein levels. The RM-ANOVA showed significant improvements in both ETG and STG groups in arm curl (both ps= 0.003) and sit to stand (p= 0.004 and p= 0.030 respectively). In addition, the ETG group was able to cover a greater distance in the 6-minute walk test than the pre-intervention (p< 0.001) and than STG group (p= 0.004). The same result emerged for the Tinetti balance and gait test, where the ETG group showed higher balance and walking ability than the pre-intervention (p< 0.001) and than STG group (p= 0.002). With regard to cognitive performance, results showed an improvement in general cognitive function (MMSE) both in the ETG group (p= 0.002) and in the STG group (p= 0.010). Another important result concerns the perception of fatigue (PFS-16), where the ETG group reported a lower fatigue than ETG (p= 0.013) and CON (p< 0.001) groups; in addition, the CON group reported a higher perception of fatigue than pre-intervention (p= 0.032). Lower serum levels of α-synuclein were observed after ETG training (p= 0.037). In contrast, higher serum levels of FGF-21 were observed after ETG training (p= 0.023). WB-EMS training is an effective and well-tolerated training strategy for Parkinson's patients. Endurance training combined with WB-EMS was more effective than strength training in improving physical fitness, cognitive performances and the level of neutrophic factors, which is correlated with an improvement in global cognitive function and severity of Parkinson's disease. The FGF plays a crucial role in the survival of neurons as well as in neuroinflammation and mitochondrial dysfunctions caused by abnormal aggregation of α-synuclein. FGF21 infact reduces the accumulation of alpha synnuclein, reducing its toxicity. Moreover, this endocrine hormone easily crosses the blood-brain barrier by simple diffusion, increasing its protection factor.File | Dimensione | Formato | |
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