Physical Activity in Advanced Parkinson's Disease: Impact ... - IOS Press

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Journal of Parkinson’s Disease 5 (2015) 85–93 DOI 10.3233/JPD-140426 IOS Press

Research Report

Physical Activity in Advanced Parkinson’s Disease: Impact of Subthalamic Deep Brain Stimulation Jean-François Daneaulta,b , Abbas F. Sadikota , Sébastien Barbat-Artigasc , Mylène Aubertin-Leheudreb,d , Nicolas Jodoine , Michel Panissete and Christian Duvalb,d,∗

a Cone Laboratory for Research in Neurosurgery, Department of Neurology and Neurosurgery, Montreal Neurolog-

ical Institute and Hospital, McGill University, Montreal, Quebec, Canada b Centre de Recherche de l’Institut Universitaire de G´ eriatrie de Montréal, Montréal, Québec, Canada c D´ epartement des Sciences Biologiques, Université du Québec a` Montréal, Montréal, Québec, Canada d D´ epartement de Kinanthropologie, Université du Québec a` Montréal, Montréal, Québec, Canada e Unit´ e des troubles du mouvement André-Barbeau, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada

Abstract. Background: Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson’s disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Objective: Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Methods: Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. Results: Our results demonstrate that PD patients’ quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. Conclusion: The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery. Keywords: Parkinson, STN, DBS, quality of life, exercise

INTRODUCTION ∗ Correspondence to: Christian Duval, PhD, Dept. of Kinanthropology, Université du Québec a` Montréal (UQAM), C.P. 8888 Succ. Centre-Ville, Montréal (Québec) Canada. H3C 3P8. Tel.: +1 514 987 3000/4440; E-mail: [email protected].

Parkinson’s disease (PD) is a progressive neurodegenerative disease that impairs quality of life (QoL) through several motor [1] and non-motor symptoms

ISSN 1877-7171/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved

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J.-F. Daneault et al. / STN DBS Impact on Physical Activity

[2]. Patients that have debilitating side-effects from medication may be candidates for deep brain stimulation (DBS), a validated therapeutic intervention for advanced PD [3]. While several brain regions can be targeted with DBS, the subthalamic nucleus (STN) has proven to be highly effective [4, 5]. In fact, numerous studies have demonstrated the efficacy of STN DBS in reducing PD-related motor symptoms as well as reducing the motor complications associated with drug treatment [4–9]. Concomitantly, others have demonstrated that STN DBS may also lead to improved QoL [10]. However, very little is known about the effect of STN DBS on voluntary motor behavior related to physical activity. For instance, a previous study observed that STN DBS improved walking pattern without modifying the volume of walking [11]. Examining the level of physical activity in PD, and the impact of surgical interventions on this behavior is necessary in order to better appreciate the challenges faced by patients as well as assess the effectiveness of those interventions in reducing these challenges. This is important as reduction in mobility and physical activity behavior promotes a sedentary lifestyle that can lead to severe co-morbidities and restricted QoL [12, 13]. In addition, there is evidence indicating that physical activity can improve motor symptoms of PD [14–20], and several non-motor symptoms, such as depression and insomnia [21]. Recent studies in animal models also suggest a role for physical activity in countering neuronal degeneration [22–24]. Interestingly, a previous study demonstrated that at the time of diagnosis, PD patients were as active as healthy individuals [25]. However, as the disease progresses, recent studies demonstrated that PD patients display a more sedentary lifestyle than healthy elderly individuals and do not meet recommended levels of physical activity [21, 26–29]. The objectives of the current study were to a) assess and compare the levels of physical activity and QoL in advanced PD patients that are candidates for STN DBS with those of age- and gender-matched controls; and

b) determine whether STN DBS positively affects the level of physical activity and QoL in those patients. SUBJECTS/MATERIALS AND METHODS Subjects Twenty patients diagnosed with idiopathic PD according to the UK Queen Square Brain Bank criteria [30] were recruited through the neurosurgical clinic of the Montreal Neurological Hospital. Patients were first evaluated while going through the selection process for bilateral STN DBS. Then, they were followed prospectively and re-evaluated 6 to 9 months postoperatively. Data from age- and gender-matched control subjects were taken from a databank for comparison. None of the control subjects were athletes or competed actively in any sport. Demographic and clinical characteristics of the participants are shown in Table 1. Note that none of the patients or controls had known co-morbidities that could significantly affect mobility. This research was approved by the institutional research ethics review board. Evaluation Patients and controls were asked to fill-out the Phone-FITT [31] questionnaire in order to evaluate their level of physical activity. They also completed the Short Form Health Survey (SF-36) so as to determine their QoL. Patients completed the questionnaires within one to three weeks prior to STN DBS surgery and then again 6 to 9 months after the intervention when DBS programming was deemed optimized by their physician. The outcome of the Phone-FITT consists of six scores related to the dimensions of physical activity (frequency, intensity, time and type). It provides a score combining frequency and duration (FD) and a score combining frequency, duration and intensity (FDI) for

Table 1 Demographic and clinical characteristics of participants

Controls PD patients

N

Gender

Age (years)

Years since diagnosis

LEDD pre-surgery (mg)

LEDD post- surgery (mg)

UPDRS III pre-surgery ON

UPDRS III post-surgery ON

UPDRS III pre-surgery OFF

UPDRS III post-surgery OFF

20 20

13M; 7F 13M; 7F

58 ± 6 58 ± 8

11 ± 4

1413.7 ± 641

765.9 ± 537∗

18.4 ± 11

12.9 ± 8∗

30.6 ± 13

15.8 ± 7∗

This table highlights the demographic and clinical characteristics of participants. Levodopa equivalent daily dose (LEDD) was calculated using the parameters of Tomlinson et al. [33]. M: Male; F: Female. UPDRS III pre-surgery scores are reported for ON and OFF medication. UPDRS III post-surgery scores are reported for ON medication/ON stimulation (ON) as well as for OFF medication/ON stimulation (OFF). Asterisks (∗ ) indicate a significant reduction between pre- and post-surgery (p < 0.05).


household activities (e.g. cleaning, washing dishes, preparing meals), recreational activities (e.g. strength and balance exercises, walking) and a combination of both types of activities (total). The SF-36 consists of eight scaled scores related to physical functioning, role limitations due to physical health, role limitations due to emotional health, energy/fatigue, emotional wellbeing, social functioning, pain and general health. Results from section II and III of the Unified Parkinson’s Disease Rating Scale (UPDRS) [32] was used to assess activities of daily living and motor impairment, respectively. Levodopa equivalent daily dose (LEDD) was computed to examine the change in medication postoperatively [33]. Surgery A two-stage frame-based DBS insertion was performed under local anesthesia. PD-related medications were withheld beginning on midnight of the day of surgery. Intra-operative micro-electrode recordings were performed for the verification of DBS lead placement (Medtronic 3387) in the STN (MicroGuide pro, Alpha-Omega Engineering, Israel). Both electrophysiological monitoring and stimulation were performed under local anesthesia. Several x-rays were also taken during the surgical procedure in order to pinpoint micro-electrode and lead placement. Final lead placement was confirmed during the procedure using the O-arm imaging system (Medtronic, Minneapolis, MN, USA) and postoperatively using magnetic resonance imaging. The 7482A extension, and Soletra, Kinetra or Activa PC pulse generators (Medtronic, Minneapolis, MN, USA) were implanted under general anesthesia. Activation of the electrodes was performed five days postoperatively and stimulation parameters were subsequently adjusted to optimize patient response. Statistical Analysis One way analysis of variance (ANOVA) with repeated measures were performed for all sub-scores of the SF-36, and Phone-FITT in order to assess whether scores from preoperative and postoperative PD patients as well as from age- and gender-matched healthy controls were significantly different. If differences were observed, Tukey’s post hoc test was used to identify those differences. To assess the impact of STN DBS on motor symptoms and activities of daily living in PD patients, paired t-tests were performed on the UPDRSII and UPDRS-III scores. LEDD pre- and post-surgery were also compared using a paired t-test. Threshold for statistical significance was set to p < 0.05.

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RESULTS Figure 1 illustrates the scores for each subsection of the SF-36 QoL questionnaire for the healthy controls, PD patients pre-surgery, and PD patients post-surgery. Repeated measures ANOVAs performed within each sub-section demonstrated a significant effect of group for the Physical functioning (F(19, 2) = 38.87, p < 0.05), Role limitation due to functional health (F(19, 2) = 29.88, p < 0.05), Role limitation due to emotional health (F(19, 2) = 14.18, p < 0.05), Energy/Fatigue (F(19, 2) = 3.26, p < 0.05), Emotional well-being (F(19, 2) = 20.63, p < 0.05), Social functioning (F(19, 2) = 52.58, p < 0.05), Pain (F(19, 2) = 3.41, p < 0.05), and General health (F(19, 2) = 15.12, p < 0.05) sub-sections. Tukey’s post hoc revealed that age- and gender-matched healthy controls had significantly higher scores in every sub-section compared to PD patients pre-surgery (p < 0.05). Tukey’s post hoc also demonstrated that age- and gender-matched healthy controls had significantly higher scores than PD patients post-surgery in every sub-section (p < 0.05) except for Energy/Fatigue and Pain (p > 0.05). This indicates that while aspects of QoL related to Energy/Fatigue and Pain were not statistically ameliorated in the intermediate term after STN DBS surgery, there was a large enough improvement that those aspects of QoL were no longer different from healthy controls after surgery. When preand post-surgery results were compared, a significant increase could only be observed in the Physical functioning sub-section of the SF-36 (p < 0.05). In keeping with this result, UPDRS-III scores were significantly improved from 18.4 ± 11 in the pre-surgery ON medication condition to 12.9 ± 8 in the post-surgery ON medication/ON stimulation condition (p < 0.05) indicating that PD patients’ best ON state improved after surgery. Significant improvements in the UPDRS-III scores were also observed from the pre-surgery OFF medication condition (30.6 ± 13) to the post-surgery OFF medication/ON stimulation condition (15.8 ± 7) (p < 0.05). It is important to note that although QoL sub-scores of PD patients only significantly improved in the Physical functioning category, there were individuals that improved substantially in each category. Figure 2 illustrates the scores for each sub-section of the Phone-FITT questionnaire for the healthy controls, PD patients pre-surgery, and PD patients post-surgery. ANOVAs performed within each sub-section demonstrated a significant effect of group in the FD household (F(19, 2) = 9.24, p < 0.05), FDI household (F(19,

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Fig. 1. This graph illustrates the mean sub-score results of the SF-36 QoL questionnaire for the Control group, the PD group pre-surgery and the PD group post-surgery. Asterisks (∗ ) indicate a significant difference in mean score for a given sub-section of the SF-36 (p < 0.05).

2) = 8.79, p < 0.05), FD total (F(19, 2) = 4.30, p < 0.05) and FDI total (F(19, 2) = 4.90, p < 0.05) sub-sections. However, no significant effect of group was observed in the FD recreational (F(19, 2) = 1.93, p = 0.10) and FDI recreational (F(19, 2) = 2.42, p = 0.10) sub-sections. However, these lack of differences have to be interpreted carefully as the power of those two tests falls short of the recommended 0.8. It is therefore possible that with an increased number of subjects, a significant difference in FD recreational and FDI recreational would emerge as paired t-tests with Bonferroni adjustments (results not shown) highlighted differences between the controls and the PD groups. Tukey’s post hoc demonstrated that age- and gender-matched healthy controls had significantly higher scores com-

pared to PD patients pre- and post-surgery in the FD household (p < 0.05) and FDI household sub-sections (p < 0.05) as well as in the FD total (p < 0.05) and FDI total sub-sections (p < 0.05). These results indicate that the physical activity behavior of patients did not improve in the intermediate term after STN DBS surgery. This is somewhat at odds with the results obtained from the UPDRS-II scores as a significant decrease from pre-surgery (12.5 ± 6.4) to post-surgery (8.8 ± 5.3) was observed. However, as for the QoL data, when examining the individual improvements in physical activity behavior, it is possible to observe patients that greatly improved in each category after STN DBS. The implication of these results are discussed in the following section.


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Fig. 2. This graph illustrates the mean sub-score results of the Phone-FITT questionnaire for the Control group, the PD group pre-surgery, and the PD group post-surgery. FD: score combining frequency and duration; FDI: score combining frequency, duration, and intensity. Asterisks (∗ ) indicate a significant difference in mean score for a given sub-section of the Phone-FITT (p < 0.05).

DISCUSSION

QoL, and Physical Activity in Advanced PD

The current study demonstrates that while STN DBS for patients with advanced PD significantly improves motor symptoms as assessed by clinical evaluations and some aspects of QoL, it had no significant impact on the physical activity behavior in the intermediate term.

Patients with advanced PD showed a reduction in physical activity participation as well as a marked decrease in QoL compared to healthy individuals. These results are in line with a previous study demonstrating that patients in the advanced stages of PD display decreased levels of physical activity [27].

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The current results also support the previously demonstrated notion that patients are not physically active and fail to meet the daily recommendation of physical activity [21, 26–29]. It is well known that participation in physical activity improves mobility in healthy elderly [34, 35] and disabled elderly individuals [36], which in turn may improve QoL. Therefore more emphasis should be placed on improving the physical activity behavior of PD patients. While a recent study failed to show an increase in physical activity behavior after an interventional program [37], involvement of occupational therapists, physical therapists and kinesiologists in the design of tailored physical activity programs may nonetheless prove beneficial to the mobility of these patients [14–20, 38]. Development of intervention strategies may improve the QoL of patients and reduce the risk of developing comorbidities associated with a sedentary lifestyle [12, 13], as well as lessen the burden placed on the health care system. Impact of STN DBS on QoL and Physical Activity The current study also demonstrates that, in the intermediate term, STN DBS significantly improves motor symptoms and some aspects of general QoL in advanced PD patients. However, this improvement in general QoL still falls short of levels observed in ageand gender-matched healthy individuals. This suggests a need to implement new treatment strategies in order to potentiate the effect of STN DBS on general QoL. In addition, the sedentary behavior of PD patients does not improve in the intermediate term with STN DBS. This is somewhat at odds with a meta-analysis that demonstrated an improvement in activities of daily living and improved quality of life with STN DBS [5]. This may stem from methodological differences. Indeed, the Phone-FITT measures the quantity of physical activity (frequency∗ duration) and intensity of this activity. In contrast, other commonly used methods that assess activities of daily living, such as the UPDRSII [32], provide more qualitative information related to impairment in performing certain tasks. This is exactly what was observed in the current study as PD patients improved their activities of daily living as assessed by the UPDRS-II, without improving their physical activity behavior as measured by the Phone-FITT. This indicates that STN DBS improves the ability to perform given physical activities, but this improved motor function may not translate to increases in physical activity behavior of PD patients. This is in line with results from a recent study of gait in PD where STN DBS

improved the pattern of gait (i.e. the functional ability to perform the task) without increasing the quantity of gait over a 7 day period [11]. Our findings cannot be explained by a lack of DBS efficacy in the PD population tested since clear improvements in motor symptoms were observed. Thus, the current results demonstrate that improved motor function does not systematically translate into improved physical activity behavior or QoL in advanced PD patients with many years of disability. It is possible that surgery failed to modify physical activity behavior in PD patients because they are ingrained in a sedentary lifestyle due to multiple factors related to chronic disease. Modifying behavior may be more difficult than improving motor symptoms. This is in line with a recent study that failed to change physical activity behavior with an intervention directly targeting this issue [37]. Since a previous study demonstrated that PD patients exhibit the same level of physical activity as healthy elderly individuals at the onset of motor symptoms [25], targeting that behavior earlier in the course of the disease or performing the surgical intervention sooner [39] could then be beneficial to the patients’ physical activity behavior and QoL. It is also possible that non-motor factors could contribute to sustained limitation of physical activity behavior after STN DBS in PD patients. For instance, mild and transient apathy can be observed after STN DBS surgery in some PD patients [40–43]. Apathy can lead to decreased activities of daily living [44], and could potentially hinder the ability of STN DBS to modify the physical activity behavior of patients. In the current study, patients’ LEDD was reduced by close to 50%, and few patients remained on agonists post-surgery. It is possible that limited motivation to be physically active contributed to the lack of improvement in physical activity behavior. In order optimize surgical outcome, patients need to be sensitized to their new potential for increased physical activities based on improved motor function, and encouraged to begin the process of changing their lifestyle habits soon after the intervention. To assist patients in this important process, the clinical team should take the necessary steps to ensure that the proper follow-ups are done with a multidisciplinary interventional team, including occupational and physical therapists, kinesiologists, and psychologists. Limitations of the Current Study First, non-motor symptoms of PD were not assessed or controlled for in the current study. While it


has previously been demonstrated that non-motor symptoms have a significant impact on QoL [45], at least some of those, namely anxiety and depression, do seem not to be associated with the level of physical activity in PD patients [29]. It is possible that the cohort of patients in the current study could have presented with non-motor symptoms that limited the impact of STN DBS on QoL and physical activity participation. Future studies should investigate this issue. Second, the questionnaires used in the current study were not PDspecific. While previous studies have shown that the SF-36 can be used in a PD population [46, 47], these studies have also demonstrated a lack of PD-specific content related to QoL in the SF-36 [46] which may in part explain the discrepancy between the results of the current study and others which have demonstrated larger effects of STN DBS on QoL [4, 5, 10, 48–50]. Thus, the results of the current study provide novel information that may reflect more on the impact of STN DBS on general QoL rather than only on PD-specific aspect of QoL. CONCLUSION Physical activity behavior of patients with advanced PD is reduced compared to healthy age- and gendermatched controls. As physical activity is interrelated with QoL, therapeutic interventions should be aimed at improving this behavior so as to lessen the burden of disease. Furthermore, despite the marked improvement in motor function following STN DBS, some aspects of QoL remain significantly impaired compared to healthy age- and gender-matched controls. Additionally, physical activity behavior is also not significantly improved following STN DBS. These results indicate a need to better understand the relationship between STN DBS and the ability/willingness to engage in physical activity in order to develop novel approaches designed to translate motor improvement following STN DBS into enhanced physical activity behavior so as to potentiate the effect of these interventions on QoL.

controls, and performed all necessary analyses. JFD performed the comparison between healthy controls and PD patients. JFD also wrote the manuscript. SBA, MAL, CD, NJ, MP and AFS contributed significantly to the review and critique of the manuscript before the final version was approved by all authors. ACKNOWLEDGEMENT STATEMENT (INCLUDING CONFLICT OF INTEREST AND FUNDING SOURCES) The authors of the present study wish to thank the participants who volunteered their time for this study. The authors would also like to thank Dr Fahd Al-Subaie for help with the clinical assessment of patients. This research was made possible by a Parkinson Society Canada Graduate Student Award (JFD) and a Canadian Institute of Health Research Doctoral scholarship (SBA). CD and MAL are supported by a Fonds de la Recherche du Québec-Santé salary grant. JFD, SBA, MAL, CD and AFS declare that they have no competing interests. NJ received research grants from AbbVie and travel grants from Teva Neuroscience. He was a lecturer for Novartis and participated in advisory boards for AbbVie. MP received research grants from Teva Neuroscience, Novartis, and Allergan. He was a lecturer for Allergan, Merz, Novartis and Teva. He participated in advisory boards for Merck, EMD Serono, Allergan, Merz, Novartis, and Teva. REFERENCES [1] [2] [3]

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