Review ArticleFatigue in Parkinson's disease
Introduction
Fatigue is one of the most common and disabling nonmotor symptoms seen in Parkinson's disease (PD) [1]. There is significant evidence that fatigue is an intrinsic symptom related to PD pathology and it may manifest early in the disease and even as a pre-motor symptom [2]. Unfortunately, it is also one of the most poorly understood and difficult to treat. Our goals in this paper are to review current evidence and highlight pertinent literature on the impact of fatigue in PD, how to define and measure fatigue in both clinical and research contexts, and potential causes and treatments of fatigue in PD. We conclude with take-home points for clinicians and priority areas for future research.
Section snippets
Prevalence and epidemiology
Increased focus on non-motor symptoms including fatigue has led to several prevalence studies. As early as 1967 Hoehn and Yahr listed fatigue as an initial symptom in 5 out of 183 cases of primary PD. [3] The first prevalence studies were published in 1993 [4], [5], and since then a number of different study designs and measurement scales have been applied in different patient populations, with a reported prevalence of fatigue between 33% and 58%, making fatigue one of the most common non-motor
Impact of fatigue on quality of life (HRQOL) and disability
Several studies have confirmed the negative impact of fatigue on HRQL in PD. In early PD, non-motor symptoms, including fatigue, may be more detrimental and activity-limiting than the motor symptoms of the disease [21], [22]. Also in cross sectional studies fatigue has shown to be closely related to impaired HRQOL, in many studies fatigue is shown to be the non-motor symptom with the highest negative effect [12], [14], [17], [23], [24], [25]. A survey of PD patients as to most bothersome
Defining and measuring fatigue in PD
Fatigue is a commonly used term and although its meaning may appear obvious, failure to precisely define what is meant by the term fatigue in clinical and research contexts has contributed to the perception that fatigue is a ubiquitous and nonspecific symptom that may arise from any condition and is difficult if not impossible to study with any rigor [28]. To address this situation, Kluger et al. proposed a unifying taxonomy for defining fatigue in clinical and research contexts based on 5
Potential causes of fatigue in PD
It remains unknown how the pathological processes underlying PD or their sequelae cause fatigue in PD. Fatigue complaints do not appear to be a simple consequence of motor symptoms as they are often seen in early PD [18], may precede motor symptoms, do not correlate with objective motor fatigability and do not reliably respond to dopaminergic or surgical therapies [2], [36], [37], [38], [39], [40], [41]. Regarding potential secondary causes of fatigue in PD, fatigue is consistently associated
Management
There are many challenges in the treatment of PD related fatigue, including the absence of a consensus of definition and classification, lack of clear understanding as to pathophysiology and a wide range of factors that may contribute to the total fatigue burden. Management is symptomatic and identifying and treating contributing factors as depression, sleep disturbances, anemia and pain is important, as is an evaluation of existing medications as many may have fatigue as a side-effect.
Pharmacologic interventions
Optimizing treatment for PD has traditionally focused on the motor-symptoms of the disease, and the possible effects on fatigue of the different pharmaceutical agents have not been extensively explored.
Non-pharmacologic interventions
The aim of the interventions is both to reduce the degree of fatigue and to help the patient cope with living with fatigue and may incorporate a range of approaches, including adequate information and support, aimed at both patients and caregivers. Even though there are few randomized, controlled trials evaluating the different non-pharmacological approaches, advice concerning exercise [71], [72], [73], nutrition, energy conservation strategies, mindfulness training and cognitive behavioral
Conclusion
Fatigue is a commonly reported symptom among PD patients which has a substantial impact on quality of life and disability. Clinicians should carefully distinguish fatigue from related symptoms (e.g. sleepiness, apathy) and screen patients for potentially treatable secondary causes of fatigue such as depression, sleep disorders and low testosterone. Although there is no evidence to support any therapeutic approach in PD, our clinical experience suggests that some patients may benefit from a
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