© Springer-Verlag Wien 2015
Aleksandar Videnovic and Birgit Högl (eds.)Disorders of Sleep and Circadian Rhythms in Parkinson’s Disease10.1007/978-3-7091-1631-9_1313. Fatigue and Sleepiness in Parkinson’s Disease Patients
(1)
Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
13.1 Introduction
13.2 Defining Fatigue
13.3 Measuring Fatigue
13.5.1 Fatigue and Sleepiness
13.5.2 Fatigue and Depression
13.6 Pathophysiology
13.7 Treatment
13.7.1 Pharmacologic Interventions
13.8 Conclusion
Abstract
The main focus of this chapter is fatigue in Parkinson’s disease (PD) patients, with particular emphasis on defining and measuring fatigue, describing the epidemiology of fatigue and associated factors, including a brief discussion of the interface between fatigue and sleepiness. Fatigue is a common non-motor symptom in PD patients, but is also a common complaint in the general population. To facilitate research of fatigue in PD it is important to clearly define the concept of fatigue and to use fatigue scales with good psychometric properties. Additionally, it is important to disentangle the effects of fatigue from the effects of other comorbid symptoms in the PD patients, such as depression and sleep problems. Fatigue and sleepiness are two distinct entities; thus, it is important to separate excessive daytime sleepiness from fatigue. Because of scant knowledge on pathophysiology and treatment, these sections are discussed briefly.
13.1 Introduction
Fatigue and sleepiness are commonly seen both in the general and clinical populations, such as Parkinson’s disease (PD) patients. Such non-motor symptoms are often under-recognized clinically [1], despite being of uttermost importance for the patients and significantly associated with worse quality of life [2–4]. For many patients and clinicians, the distinction between fatigue and sleepiness is unclear, as there is no clear definition of these concepts, and no consensus on what is normal or pathological. Terms such as fatigued, tired, and sleepy are used interchangeably; while fatigue can be described as an individual’s feeling of abnormal tiredness, sleepiness is defined as a tendency to fall asleep. Sleepiness and fatigue frequently co-occur in PD patients; however, it is suggested that they should be regarded as distinct symptoms that must be understood and managed separately [5]. The main focus of this chapter is fatigue, with particular emphasis on defining and measuring fatigue, describing the epidemiology of fatigue and associated factors, including a brief discussion of the interface between fatigue and sleepiness. Finally, the pathophysiology and treatment of fatigue in PD patients are briefly discussed.
13.2 Defining Fatigue
There are two types of fatigue, peripheral fatigue (fatigability) and central fatigue. Fatigability is objectively measured and involves lack of energy associated with repetitive muscular movements. The main focus of this chapter will be on central fatigue, which is a subjective feeling, and thus, objectively immeasurable. There is no universally accepted definition of this type of fatigue, and the division between pathological and normal fatigue is unclear [6]. Focus groups of PD patients operationalized fatigue as abnormal tiredness [7], interfering with normal function. The fatigue experienced by the PD patient is different from the fatigue experienced before developing the disease [7].
Fatigue can be described as physical or mental fatigue [6]. Physical fatigue is the subjective feeling of being exhausted and lacking energy, including muscle weakness, despite being able to perform the tasks. Mental fatigue is the subjective feeling of being mentally exhausted, including difficulty concentrating and lack of mental clarity during and after periods of cognitive strain. It is suggested that mental and physical fatigue are independent of each other [8], as they are not correlated. If the fatigue is persistent over 6 months, it can be defined as chronic fatigue [9]. In patient populations with stable diseases, the concept of chronic fatigue is useful, as it helps to separate acute and transient fatigue from fatigue that is stable over time.
Fatigue can be categorized as primary or secondary fatigue. Primary fatigue is related to the neurologic disease itself, while secondary fatigue is caused by other factors such as infections, anemia, endocrine dysfunction, depression, sleep disturbance, or side effects of the medications. It may be difficult to disentangle these two issues; during a clinical investigation, it is important to rule out fatigue from secondary causes. In research, it is important to define what type of fatigue one seeks to measure.
13.3 Measuring Fatigue
A variety of questionnaires have been developed to measure fatigue and assess its severity, both for clinical and research purposes [10]. These questionnaires encompass different properties, such as being one- or multidimensional, and generic versus disease-specific. A one-dimensional fatigue scale condenses a range of symptoms into a single score. A multidimensional scale incorporates several aspects of fatigue [11]; for example, being able to distinguish between mental and physical fatigue [12]. A generic scale can be used to assess fatigue within the general population, while the use of a disease-specific instrument may better reflect the consequences of disease, such as PD.
As the questionnaires have varying properties, it may be that measurements from different questionnaires yield prevalence estimates that vary. In fact, a comparison between the Fatigue Severity Scale (FSS) and the Functional Assessment of Chronic Illness Therapy—Fatigue scale (FACIT-F)—concludes that they do not appear to measure identical aspects of fatigue [13].
The International Movement Disorder Society has rated all instruments used to measure fatigue in PD [14]. For screening purposes, recommended scales include the FSS, FACIT-F, and the Parkinson Fatigue Scale (PFS) [14]. The Committee suggested further examinations of psychometric properties of the scales, including sensitivity and specificity.
An example of a generic unidimensional scale is the FSS [15], which is probably the most widely used fatigue instrument. The FSS does not distinguish between different aspects of fatigue; and what aspect of fatigue measured is not defined. The FSS is a nine-item instrument; each statement is rated on a scale of 1–7. The individual score is the mean of the numerical responses. A cutoff of four is used to distinguish between fatigued and non-fatigued, but other cutoffs have also been suggested. The psychometric properties of the FSS in PD are good [14].
The Parkinson Fatigue Scale is a PD-specific scale, developed to assess fatigue in PD patients [7]. The scale is unidimensional, encompassing physical fatigue. The focus of the instrument is to distinguish between PD patients who report having fatigue versus not, and between problematic and non-problematic levels of fatigue [7]. Its psychometric properties, including reliability, are good [14].
The FACIT-F scale is another widely used instrument, available in many languages and freely available (http://www.facit.org). While it does not define the type of fatigue it aims to assess, it covers both the experience and impact of fatigue. It consists of 13 items, with 5 response categories, yielding a sum between 0 and 52. The FACIT-F is reported to have good psychometric properties, including data quality, validity, and reliability [14].
One questionnaire not included in the rating by the International Movement Disorder Society is the Fatigue Questionnaire (FQ). The FQ is widely used in cancer research [7], and is an example of a multidimensional fatigue questionnaire that distinguishes between mental and physical fatigue [12]. The FQ also contains two additional items about the duration and extent/impact of disease, enabling the identification of cases with chronic fatigue. The FQ was originally validated in primary care, and has demonstrated good face-and discriminate validity, as well as stable psychometric properties across populations [12].
13.4 The Epidemiology of Fatigue in PD Patients
The prevalence of fatigue in PD patients is found to range between 32 and 70 %, depending on the population examined, the definition of fatigue and the instrument used to measure fatigue (reviewed in [16]). Most of these studies involved small clinical cohorts. Using a population-based cohort approach, two studies have estimated the prevalence of fatigue of 28 % (chronic fatigue, FQ) [17] and 44 % (measured by Nottingham health profile) [18]. This prevalence is likely an underestimation, since studies have not included PD patients who are unable to utilize self-report instruments.
Many of the studies mentioned above have examined whether PD patients experience higher levels of fatigue than those without PD, often using clinical populations. Comparison between PD patients and patients without PD is important as fatigue is common in the general population; one estimation is that 18 % of general population over the age of 65 years experience fatigue (measured as chronic fatigue) [19]. However, clinical populations may have even higher levels of fatigue than the general population, resulting in an underestimation of the importance of fatigue in PD compared with disease-free individuals. Available population-based studies that compared fatigue in the PD population with the general population found significantly higher prevalence of fatigue among PD patients [17, 18].
Women usually report higher levels of fatigue than men in the general population [19]. Examining gender-specific differences, therefore, may be of importance. Few studies have investigated gender differences in PD [16], and results have been inconsistent. One recent study found no evidence of gender differences in fatigue [20], while two earlier studies found a trend towards significantly higher levels of fatigue in women [21] and a significantly higher prevalence of fatigue in women [17].
Most cross-sectional studies reported an association between PD severity and progression and fatigue [17, 20, 22], while others did not confirm these associations [8, 18]. Data from a longitudinal study of a community-based PD cohort reported an increasing lifetime prevalence of fatigue over time [23], and fatigue being related to disease severity. Persistence of fatigue has also been shown to vary, with half of all PD patients experiencing persistent fatigue.
13.5 Factors Associated with Fatigue in PD Patients
Some PD patients have fatigue only, with the absence of other non-motor symptoms [23]. Among patients without sleep problems, depression, and dementia, 43.5 % reported fatigue. Comorbid non-motor symptoms are, however, very common. Among 100 patients who reported the presence of sleep disturbance, depression, anxiety, fatigue or sensory symptoms, 59 % had two or more symptoms, 23 % had four or more, and 11 % had all five symptoms [22]. Thus, it is important to disentangle the effects of the different non-motor symptoms in PD patients, as they are associated and may contribute to secondary fatigue. Here, we focus on sleepiness and depression.
13.5.1 Fatigue and Sleepiness
There has been some focus on the overlap of fatigue and sleep problems, such as sleepiness (or daytime somnolence) in PD patients. Interestingly, while sleep problems overall, as measured by the unidimensional disease-specific Parkinson’s Disease Sleep Scale, are significantly associated with fatigue [24, 25], studies assessing daytime sleepiness (using Epworth Sleepiness Scale ) generally have not found an association with fatigue [20, 21, 26]. This suggests that fatigue is a distinct entity from sleepiness, as measured by the ESS. Additionally, there are differences in the way fatigue and sleepiness are correlated with other factors such as dopaminergic treatment and depression [27]. This is further underlined by the finding that modaphenil has an effect in treating sleepiness (reviewed in [28]), but not fatigue (reviewed in [29]). Thus, it is important to separate excessive daytime sleepiness from fatigue.
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