Physical Activity and Neuropsychiatric Symptoms of Parkinson Disease

Abstract

Neuropsychiatric symptoms of Parkinson disease (PD) such as fatigue, depression, and apathy are common and detract from quality of life. There is little published on the impact of physical activity on the neuropsychiatric symptoms of PD. A convenience sample of 45 patients with PD (mean age = 66.1 years; 33% female) completed questionnaires on physical activity, neuropsychiatric symptoms, and specific exercise preferences. Covarying for age and gender, higher levels of physical activity were associated with significantly less fatigue, as well as a trend for less apathy and depression and greater positive affect. Exercise preferences included moderate intensity (73%), at home (56%), in the morning (73%), scheduled (69%), options for varied activities (73%), and preference for both structured/supervised (50%), and unsupervised/self-paced (50%) programs. Preferred activities included the use of aerobic exercise equipment, resistance training, and yoga. Developing and tailoring exercise programs that incorporate specific preferences may result in more effective interventions for patients with PD.

Keywords

Parkinson disease mental health movement disorder

Introduction

Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. Approximately, 1% to 2% of the population more than 50 years old has PD, which equals approximately 1 million affected persons. Parkinson disease is characterized by 3 cardinal motor symptoms which include bradykinesia, rigidity, and tremor. In addition to these motor symptoms, PD is also characterized by neuropsychiatric symptoms including cognitive impairments,¹ sleep disturbances,² depression, anxiety, fatigue, and apathy.³ Parkinson disease is a progressive condition that worsens with time, and treatment options primarily consist of pharmacotherapy for motor symptoms.

While neuropsychiatric symptoms of PD are highly prevalent, they often go unaddressed and play a significant role in patients’ quality of life. In fact, neuropsychiatric symptoms of PD contribute more negatively to health related-quality of life than motor symptoms (eg⁴). There is some indication that antidepressant medication is less effective in treating depressive symptoms among patients with PD, compared to non-PD patients.⁵ Similarly, pharmacologic interventions with patients with PD may result in worsening of cognitive functioning. Therefore, given the potential side effects of pharmacological interventions and possible interactions with other medications, particularly in the elderly individuals, nonpharmacological approaches to addressing these issues are preferred.³

Interventions to address neuropsychiatric symptoms in patients with PD are sorely needed. Increasing leisure-time physical activity in patients with PD may be an effective nonpharmacologic approach to decreasing neuropsychiatric symptoms and improving the quality of life in these patients. Thus far, exercise intervention for patients with PD has focused on improving physical functioning with very few examining the potential effects on neuropsychiatric symptoms. The majority of these reported exercise intervention studies consist of patients with PD engaging in specific, targeted exercises in the context of physical therapy with a physiotherapist. In a recent meta-analysis, Goodwin and colleagues⁶ identified 14 randomized controlled trials of exercise interventions for patients with PD. Only 3 studies incorporated an aerobic component and most were designed to target trunk strength, balance, gait, and flexibility. In all cases, these exercise interventions were designed as “therapy” for motor problems rather than more generally increasing leisure-time physical activity in daily living.

As evidenced by studies with non-PD patients, physical exercise (and aerobic exercise, specifically) greatly benefits the type of neuropsychiatric symptoms commonly experienced by patients with PD.⁷ Exercise studies conducted with non-PD patients may be utilized as a guide to hypothesize that aerobic exercise may indeed play an important role in improving the neuropsychiatric symptoms of PD. For example, physical activity interventions have been examined and found to be highly effective at reducing fatigue in patients with a variety of other medical conditions including multiple sclerosis,⁸ systemic lupus erythematosus,⁹ heart failure,¹⁰ and chronic fatigue syndrome.¹¹ Therefore, it may be the case that higher levels of physical activity in patients with PD would have a beneficial effect on reducing fatigue.

Second, aerobic exercise decreases depression^12

–15 in non-PD patients just as well as behavioral therapy¹⁶ and pharmacotherapy.¹⁷ For example, in a review, Dunn and colleagues¹⁸ reported that a number of quasi-experimental studies as well as randomized controlled trials demonstrated an effect of exercise for reducing depressive symptoms by at least 50% by the end of the intervention. A substantial portion (30%-40%) of patients with PD exhibit depressive symptoms.^19
–21 Therefore, increased physical activity may serve to decrease depressive symptoms among patients with PD.

Also, aerobic exercise improves various affective states (eg,^22,23). The positive reinforcing properties of exercise are potentially mediated by its effects on the endogenous opioid system and by dopaminergic reinforcement mechanisms.²⁴ In addition, exercise has been found to result in acute improvements in mood (eg,^23,25,26). In fact, more recent exercise intervention studies^22,23,
27 have shown that while decreases in negative affect were not found, significant increases in positive affect were demonstrated. Therefore, patients with PD may find engaging in physical activity to be a viable means of experiencing pleasurable mood states, such as increased positive affect while experiencing decreases in negative mood states such as apathy and negative affect.

The development of physical activity interventions for specific patient populations (eg, cancer, depression, and diabetes) has received increased empirical attention over the last decade. As exercise research in this area increases, concurrent examination of exercise preferences has been conducted in an effort to more effectively develop interventions that promote increased adherence, quality of life, and symptom reduction. Studies examining exercise preferences have often considered, but have not been limited to, interest for participating in a program, type of exercise, intensity of activity, location, company (ie, alone or with others), extent of supervision, structure, and duration of exercise.^{28

–37} Results of these studies have shown specific associations between exercise preferences and demographic factors as well as disease-specific characteristics. For example, patients having undergone cancer treatment and particularly those in palliative care often prefer exercise that is home based and conducted alone with family, friends, or other cancer survivors.^30,37,38

The purpose of this study is 2-fold. First, the relationship between neuropsychiatric symptoms of PD and levels of physical activity will be examined. We hypothesize that lower levels of physical activity will be associated with greater neuropsychiatric symptoms of PD including fatigue, depression, and such affective states as apathy and positive/negative affect. Second, the extent to which patients with PD are interested in engaging in a program of physical activity as well as their specific exercise preferences will be examined. By tailoring physical activity interventions to patients’ preferences, the effectiveness of and adherence to an exercise intervention may be increased.

Methods

Procedure

Participants were recruited from a Movement Disorders Clinic in a psychiatric hospital located in the Northeast United States from June 2010 to November 2010. The Movement Disorders clinic sees approximately 750 patients (47% female, mean age 67.4 years) per year, and 67% of these patients are being treated for PD. The hospital’s Internal Review Board approved study procedures and methods. The second author, the Director of the Movement Disorders Clinic, identified patients who were both interested in participating in the study and who met the following inclusion criteria (a) between 18 and 80 years of age; (b) currently engaged in PD treatment; and (c) in stages 1 to 3 (Hoehn and Yahr staging) of PD. Patients were excluded if they had (a) a history of psychotic disorder or current psychotic symptoms; (b) current suicidality or homicidality; (c) marked cognitive impairment according to a Mini-Mental Status Examination score of <24; (d) significant physical disabilities or medical problems such as cancer requiring treatment in past 5 years; myocardial infarction or cerebrovascular accident within the past 6 months; unstable angina within the past 6 months; uncontrolled hypertension; congestive heart failure; history of musculoskeletal problems that limit walking; history of significant kidney or liver disease.

The second author described the research study and, if the patient expressed interest in the study, obtained permission to have a member of the research staff contact the patient for further eligibility and inclusion into the study. A research assistant contacted interested patients and carefully explained all aspects of the study, including the potential risks and benefits and the expected duration and time commitment of their participation. Interested participants were scheduled for an assessment session. During this appointment, a research assistant read aloud and recorded participant responses to all the questions of questionnaires assessing demographic and clinical characteristics as well as past and current exercise behaviors and preferences.

Measures

Demographic characteristics

Information was collected regarding participants’ age, sex, level of education, marital status, employment status, and level of income.

International Physical Activity Questionnaire

To understand patterns of physical activity, the short 7-day recall version of the International Physical Activity Questionnaire (IPAQ) was administered. Participants were asked to report the number of minutes/day and number of days/week they engage in vigorous-intensity activity, moderate-intensity activity, and walking in the week prior to study participation. This version of the IPAQ contains 7 items and has been shown to have good psychometric properties.³⁹

Exercise preferences

Exercise preference items were adapted from work with^30,
36,
38 cancer patients. Participants in this study were asked their exercise preferences for the following: (1) type of activity (eg, walking, running, gym equipment, swimming, organized sport), (2) time of day (morning, afternoon, or evening), (3) company (alone, with others in drug treatment, with family), (4) location (home, community fitness center, outside), (5) intensity (low, moderate, vigorous), and (6) structure (supervised vs self-paced, scheduled vs spontaneous/flexible). In addition, participants were also asked about whether they would have wanted to discuss how to incorporate physical activity into their leisure time as well as whether they would be interested in participating in an exercise program if it were offered to them.

Apathy Scale (AS; 40)

The AS consists of 14 self-report items that are phrased as questions and are answered on a 4-point Likert-type scale (0 = not at all to 3 = a lot). In a recent review of apathy scales used in Parkinson research, the AS was identified as “recommended” for screening and assessing the severity of apathy in patients with PD.⁴⁰ Scores ≥14 are considered apathetic.

Parkinson Fatigue Scale (PFS-16; 41)

The PFS-16 is a 16-item self-report measure of patients’ subjective experience of fatigue over the last week. Patients are asked to rate the extent to which each statement describes their feelings and experiences. The 5 response options range from strongly disagree to strongly agree. The PFS-16 has demonstrated satisfactory test–retest reliability and good specificity and sensitivity.⁴¹ An overall fatigue score was calculated by obtaining the mean score across the 16 items.

Primary Health Questionairre 9 (PHQ-9)

The PHQ-9 was designed to assess the severity of depressive symptoms.^42–44 The psychometric properties of the PHQ-9 have been established in various clinical research samples. Scores ranging from 5 to 9 reflect minimal symptoms, 10 to 14 suggest mild depression, 15 to 19 reflect moderate depression, and scores ≥20 are indicative of severe depression.

Positive and Negative Affect Schedule (PANAS; 45)

The PANAS is a 20-item self-report scale that has demonstrated good reliability and validity and was used to assess positive and negative mood.

Statistical Analysis Plan

First, descriptive statistics (ie, means and prevalence) of basic demographic and clinical characteristics of the sample were summarized. These demographic and clinical characteristics were then examined in relation to the levels of physical activity and neuropsychiatric symptoms with the use of t tests and correlations. Next, the relationship between neuropsychiatric symptoms and levels of physical activity were initially examined by conducting correlations between variables and then with regression models. Given our expected direction of association between variables, correlations were conducted with 1-tailed tests. We used ordinary least squares regression models to evaluate the strength of relationships between neuropsychiatric symptoms and physical activity, our primary dependent variable. All models included age and gender as planned covariates, given the significant relationships with physical activity and neuropsychiatric symptoms. A planned series of models evaluated individual symptom indices (ie, apathy, negative affect, positive affect, depression, and fatigue) in covariate adjusted models and in a multivariable model designed to evaluate unique contributions across these related neuropsychiatric symptoms. No selection methods were employed. All variables selected for the current study were designed to index common neuropsychiatric symptoms thought to be related to physical activity. Given large correlations between neuropsychiatric symptoms, multicolinearity was determined by examining variance inflation factors where values greater than 10 are considered to be of concern and would be eliminated from the model.⁴⁶ Lastly, means and percentages were utilized to summarize participant exercise preferences. Analyses were conducted utilizing SPSS version 20 and statistical significance was set at P < .05.

Results

Patient Characteristics

Forty-five patients with PD (66.7% male; mean age of 66.1 years, SD = 7.6 years) were enrolled in the study. Table 1 lists the demographic and clinical characteristics of the sample. Age and gender were examined in relation to neuropsychiatric symptoms. Only negative affect (15.9 vs 11, males vs females, t = 3.27, df = 43, P < .01) was found to differ between males and females. Older participants were significantly less likely to experience fatigue (r = −.31, P < .05) and depression (r = −.45, P < .01). Participants were fairly active in the week prior to study participation, reporting a median of 540 minutes of physical activity during the week (includes a median of 150 min/week walking, 180 min/week of moderate-intensity activity, and 60 min/week of vigorous-intensity activity).

Table 1.

Sample Characteristics (N = 45)

Clinical Characteristics	Mean or Percent of Sample (N = 45)	SD
Demographic characteristics
Age (years)	66.1	7.6
% Male	66.7%
% Caucasian	95.6%
% Married	82.2%
% Some college education	78%
Employment status
Unemployed	2.2%
Employed part time	11.1%
Employed full time	15.6%
Retired	71.1%
Neuropsychiatric symptoms
Apathy	10.76	6.85
Fatigue	45.38	15.76
Depression	14.51	5.23
Positive affect	34.76	7.86
Negative affect	14.58	5.14
Physical activity
Exercise program (% of sample)	57.8%
Total minutes of physical activity per week (Median)	540 minutes

Relationship Between Neuropsychiatric Symptoms of PD and Levels of Physical Activity

See Table 2 for the correlations between neuropsychiatric symptoms and level of physical activity (total number of moderate-to-vigorous activity minutes per week). Fatigue (r = −.35, P < .05) and positive affect (r = .27, P < .05) were significantly correlated with level of physical activity. In addition, apathy (r = −.25; P = .05) and depression (r = −.20, P = .09) were marginally associated with the level of physical activity. Individual regression models controlling for age and gender revealed a significant association between level of physical activity and fatigue (β = −.411, t = −2.709, df = 44, P < .05). Level of physical activity was also marginally associated with apathy (β = −.258, t = −1.706, df = 44, P = .09), depression (β = −.294, t = −1.712, df = 44, P = .09), and positive affect (β = .265, t = 1.763, df = 44, P = .085). In a multivariate regression model that included all marginally significant neuropsychiatric symptoms (P < .10) that controlled for age and gender, only fatigue emerged as marginally significant (β = −.355, t = 1.698, df = 44, P = .098; see Table 3). Examination of variance inflation factor (VIF) values revealed no serious concerns of multicolinearity (ie, all values were less than 10) and thus no symptoms were removed from the model.

Table 2.

Correlations Between Neuropsychiatric Symptoms and Levels of Physical Activity

	Fatigue	Apathy	Depression	Positive Affect	Negative Affect	Physical Activity Minutes
Fatigue	1.00
Apathy	.46^c	1.00
Depression	.65^d	.42^c	1.00
Positive affect	−.54^d	−.60^d	−.57^d	1.00
Negative affect	.36^b	.47^c	.50^d	−.37^b	1.00
Physical activity minutes^a	−.35^b	−.25	−.20	.27^b	−.18	1.00

^aModerate-to-vigorous physical activity minutes.

^b P < .05.

^c P < .01.

^d P < .001, from 1-tailed tests.

Table 3.

Summary of Multivariate Regression Model

	B	SE B	β	VIF
DV: moderate-to-vigorous physical activity
Age	−10.10	14.15	−.134	1.61
Gender	213.94	193.55	.178	1.19
Fatigue	−12.91	7.6	−.355^a	2.00
Apathy	−4.93	16.60	−.059	1.80
Depression	−1.47	26.41	−0.13	2.66
Positive Affect	1.93	16.35	.026	2.31

Abbreviation: VIF, variance inflation factor.

^a P < .1.

Exercise Preferences

Table 4 lists specific exercise preferences of participants. There were high levels of interest in discussing physical activity as well as potentially engaging in a physical activity program for patients with PD. In addition, a majority of patients stated that they would be physically able to engage in exercise. Participants did not express strong preferences for whether they engaged in physical activity with others or alone but reported a preference for exercising at home, in the morning, and at a moderate intensity. They preferred their activities to be scheduled, conducted in long bouts, and with varied options for type of activity. In addition, most participants (86.7%) were interested in including resistance training and all (100%) reported being willing to wear a pedometer to self-monitor step counts.

Table 4.

Specific Exercise Preferences of Patients With Parkinson Disease

Exercise Preference	Percent of Sample
1. Would you want to discuss how to develop your own leisure-time physical activity program?
Yes	82.2%
No	8.9%
Maybe	8.9%
2. If a leisure-time physical activity program designed for persons with Parkinson disease were offered to you, would you be interested in participating?
Yes	91.1%
No	0%
Maybe	8.9%
3. Would you be physically able to participate in a leisure-time physical activity program designed for persons with Parkinson disease?
Yes	80.0%
No	2.2%
Maybe	17.8%
4. With whom would you prefer to exercise?
Alone	20.0%
With others	37.8%
No preference	42.2%
5. Where would you prefer to exercise? (More than one preference allowed)
Home	55.6%
Gym/YMCA	31.1%
At our hospital fitness facility	22.2%
Outside	28.9%
No preference	13.3%
6. What time of day would you prefer to exercise?
Morning	73.3%
Afternoon	13.3%
Evening	8.9%
No preference	4.4%
7. What intensity would you prefer your exercise program to be?
Low intensity (eg, taking a leisurely stroll)	13.3%
Moderate intensity (eg, brisk walk)	73.3%
High intensity (eg, running)	11.1%
No preference	2.2%
8. What type of activities would you like to perform?
Same exercise each session	26.7%
Different exercise each session	73.3%
9. How would you prefer to perform these exercises?
Supervised/instructed	50%
Unsupervised/self-paced	50%
10. How would you prefer to engage in physical activity?
In one long bout of exercise (30-60 minutes)	68.9%
In short bouts throughout the day when you can fit them in (10 minutes each time)	20.0%
No preference	11.1%

When patients were asked their level of interest in various types of exercise programs and components, there appeared to be fairly high level of interest in most types (see Figure 1). Highest level of interest was for the use of recumbent bikes (mean = 4.4, SD = 0.98; where 1 = definitely not interested to 5 = definitely interested), followed closely by treadmill walking (mean = 4.2, SD = 1.1) and resistance training (mean = 4.0, SD = 1.0).

Figure 1.

Level of Interest Type of Exercise Programs.

Discussion

The results of this study highlight the relationship between higher levels of physical activity and lower levels of neuropsychiatric symptoms. Of the various neuropsychiatric symptoms, fatigue emerged as the most strongly related to level of physical activity, although the strength of this effect diminished when the other neuropsychiatric symptoms were included in the model. In other work, both correlational⁴⁷ and prospective⁴⁸ studies have demonstrated the inverse relationship between severity of fatigue and level of physical activity in patients with PD. This relationship is also true across many chronic illnesses, where fatigue is either a symptom or a consequence of treatment. Persoon and colleagues⁴⁹ describe a negative cycle whereby fatigue contributes to muscle deconditioning and lower cardiorespiratory fitness. This, in turn, results in the inability to fully engage in life’s everyday activities (eg, carrying groceries up the stairs)—thus, significantly impacting quality of life.

Consistent with the existing literature, we also found strong correlations between individual neuropsychiatric symptoms, particularly between fatigue and depression. Fatigue is a symptom of a major depressive disorder and therefore depressive symptoms may be a confounder when examining the relationship between fatigue and physical activity. However, examination of the VIFs in this study did not reveal strong concern for multicolinearity. Indeed, others have reported that depression and fatigue are independently related to PD evidenced by the high rates of fatigue among patients with PD, even in the absence of depression.⁵⁰ Also, depression is not always consistently associated with fatigue when mental (ie, amount of effort an individual feels they need to expend in order to pay attention to tasks) and physical fatigue (ie, amount of perceived effort needed to perform activities requiring skeletal muscles such as walking, lifting, etc) are distinguished. For example, Lou and colleagues⁵¹ found that depression was significantly associated with all dimensions of fatigue measured with the Multidimensional Fatigue Scale, except physical fatigue.

Of note, the items of the Parkinson’s Fatigue Scale, the current study’s measurement of fatigue, are primarily focused on the physical aspects of fatigue. It is possible had we examined mental fatigue, its correlation with depression would be even higher than that of physical fatigue. However, we would expect that level of physical activity would also be inversely related to mental fatigue as well, particularly given the cognitive benefits associated with exercise in older adults (eg,²²). Indeed, Elbers and colleagues⁴⁸ found that mental fatigue was associated with lower levels of physical activity among a large sample of patients with PD. Future studies should continue to examine these different facets of fatigue in relation to physical activity in patients with PD more thoroughly.

Given the results of this study, along with previous work, a logical next step in this area of research would involve the development of physical activity interventions to address neuropsychiatric symptoms in patients with PD. While physical activity interventions have demonstrated efficacy in decreasing fatigue in other chronic conditions,^11,
52 they have been relatively unexplored in patients with PD with fatigue. In one study,⁵³ 39 participants with PD were randomized to either a community exercise program or a control condition. Consistent with the current findings, participants in the study with higher levels of fatigue were less active. However, the weekly exercise intervention was not effective in reducing fatigue. One possible explanation for this finding was an inadequate dose of exercise, since participants engaged in an average of 15 exercise sessions over 12 weeks. This equates to 1 to 2 days/week of exercise which is much lower than the levels of physical activity observed in intervention studies targeting decreases in fatigue in patients with other non-PD conditions.⁵² In another recent small randomized study, patients with PD who received a 6-week, home-based treadmill exercise program that consisted of 20 to 40 minutes of exercise 4 days a week showed statistically significant decreases in fatigue at posttreatment.⁵⁴ Therefore, this literature is still in its infancy and more rigorously designed, well-controlled clinical trials are necessary.

In an effort to help inform the development of physical activity interventions for this population, we also assessed specific exercise preferences of patients with PD. Most participants expressed an interest in engaging in an exercise program for patients with PD. Exercise preferences included moderate intensity, at home, in the morning, scheduled, options for varied activities, and preference for both structured/supervised and unsupervised/self-paced programs. Preferred activities included the use of aerobic equipment, resistance training, and yoga. As such, exercise programs that incorporate varied opportunities to remain active may be a particularly good fit for the PD patient population. Once such program to consider may be a lifestyle physical activity program. Dunn, Andersen, and Jakicic⁵⁵ define lifestyle physical activity as “daily accumulation of at least 30 minutes of self-selected activities, which include all leisure, occupational, or household activities that are at least moderate to vigorous in their intensity and could be planned or unplanned activities that are part of everyday life.” These types of physical activity interventions have the advantage of being cost effective and flexible enough to meet the individual needs of patients.

There are a number of study limitations that merit discussion. First, the small convenience sample (n = 45) is likely not a representative of patients with PD but rather patients from a single clinical practice. It is likely that those who expressed interest in this study were already engaging in some level of physical activity. In addition, there have been reports that the IPAQ may overestimate self-reports of physical activity.⁵⁶ However, despite this, we found a relationship between the extent of physical activity and neuropsychiatric symptoms among patients with PD. Future studies should determine the rates of physical activity involvement in a larger, representative sample of patients with PD, utilizing objective measures of physical activity in this study. Although not examined in the current study, future work should explore the relationship between levels of physical activity and important determinants of disease severity, disease duration, and specific treatment approaches. Lastly, this is a cross-sectional study and therefore any significant findings should not be considered causal but rather indicative of potential relationships that should be further explored within a longitudinal design in future studies.

Conclusions

Patients with PD have numerous and highly prevalent neuropsychiatric symptoms that are negatively related to physical activity levels. Fatigue, in particular, emerged as the symptom most strongly related to level of physical activity. As with other chronic conditions, developing physical activity interventions to address fatigue may prove efficacious. The specific exercise preferences identified in the current study may help to inform these intervention development efforts.

Footnotes

Authors’ Note

This work was conducted at Butler Hospital in Providence, Rhode Island, and presented at a scientific meeting: Abrantes AM, Friedman JH, Brown RA, Strong DR, Gutierres J, Ing E, Rogers J, and Riebe D. Physical activity and nonsssmotor symptoms of Parkinson’s Disease. Poster presented at the 32nd Annual Meeting & Scientific Sessions of the Society of Behavioral Medicine, Washington, DC; April 2011.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Friedman lectures for Teva, Ingelheim Boehringer, and General Electric. He has consulting relationships with United Biosource, Bubaloo, Halsted, Reitman LLC, EMD Serono, Genzyme, Teva, Acadia, Addex Pharm, Schwarz Pharma, and Roche. Dr. Friedman also received royalties from Demos Press.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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