Review Article
Fatigue in Parkinson's disease

https://doi.org/10.1016/j.jns.2016.12.061Get rights and content

Highlights

  • Fatigue is one of the most common and disabling nonmotor symptom seen in Parkinson's disease.

  • A unifying taxonomy for defining fatigue in PD is presented.

  • Potential causes of fatigue in PD are discussed.

  • Interventions, both pharmacologic and non-pharmacologic are reviewed.

Abstract

Fatigue is one of the most common nonmotor symptoms in Parkinson's disease and may affect a wide range of everyday activities, cause disability and reduce quality of life. It occurs at every stage of PD, and once present will often persist and may worsen over time. Lack of a consensus of definition and classification, and a range of different self-reporting scales has so far made the study of fatigue challenging. We review a unifying taxonomy for defining fatigue in clinical and research contexts as well as case definition criteria for PD-related fatigue. The potential causes of fatigue in PD are discussed as are recommendations for treatment.

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

References (77)

  • K.L. Chou et al.

    Neuroimaging and clinical predictors of fatigue in Parkinson disease

    Parkinsonism Relat. Disord.

    (2016)
  • M. Capecci et al.

    Rest energy expenditure in Parkinson's disease: role of disease progression and dopaminergic therapy

    Parkinsonism Relat. Disord.

    (2013)
  • G. Kenangil et al.

    The relation of testosterone levels with fatigue and apathy in Parkinson's disease

    Clin. Neurol. Neurosurg.

    (2009)
  • O. Rascol et al.

    A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes

    Lancet Neurol.

    (2011)
  • S. Rios Romenets et al.

    Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson's disease—a randomized study

    Parkinsonism Relat. Disord.

    (2013)
  • W.G. Ondo et al.

    Memantine for non-motor features of Parkinson's disease: a double-blind placebo controlled exploratory pilot trial

    Parkinsonism Relat. Disord.

    (2011)
  • A.K. Cashion et al.

    National Institutes of Health Symptom Science Model sheds light on patient symptoms

    Nurs. Outlook

    (2016)
  • J.H. Friedman et al.

    Fatigue in Parkinson's Disease: Report From a Mutidisciplinary Symposium, NPJ Parkinson's Disease 2

    (2016)
  • C. Pont-Sunyer et al.

    The onset of nonmotor symptoms in Parkinson's disease (The ONSET PD Study)

    Mov. Disord.

    (2014)
  • M.M. Hoehn et al.

    Parkinsonism: onset, progression and mortality

    Neurology

    (1967)
  • J. Friedman et al.

    Fatigue in Parkinson's disease

    Neurology

    (1993)
  • J.J. van Hilten et al.

    Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease

    J. Neural Transm. Park. Dis. Dement. Sect.

    (1993)
  • K. Karlsen et al.

    Fatigue in patients with Parkinson's disease

    Mov. Disord.

    (1999)
  • K. Abe et al.

    Fatigue in patients with Parkinson's disease

    Behav. Neurol.

    (2000)
  • L.M. Shulman et al.

    Comorbidity of the nonmotor symptoms of Parkinson's disease

    Mov. Disord.

    (2001)
  • K. Herlofson et al.

    Measuring fatigue in patients with Parkinson's disease - the Fatigue Severity Scale

    Eur. J. Neurol.

    (2002)
  • G. Schifitto et al.

    Fatigue in levodopa-naive subjects with Parkinson disease

    Neurology

    (2008)
  • P. Barone et al.

    The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease

    Mov. Disord.

    (2009)
  • F.O. Goulart et al.

    Fatigue in a cohort of geriatric patients with and without Parkinson's disease

    Braz. J. Med. Biol. Res.

    (2009)
  • D.A. Gallagher et al.

    What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them?

    Mov. Disord.

    (2010)
  • A.G. Beiske et al.

    Fatigue in Parkinson's disease: prevalence and associated factors

    Mov. Disord.

    (2010)
  • P. Martinez-Martin et al.

    The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease

    Mov. Disord.

    (2011)
  • H. Miwa et al.

    Fatigue in patients with Parkinson's disease: impact on quality of life

    Intern. Med.

    (2011)
  • K. Herlofson et al.

    Fatigue in early Parkinson's disease. Minor inconvenience or major distress?

    Eur. J. Neurol.

    (2012)
  • J.H. Friedman et al.

    Fatigue in Parkinson's disease: a nine-year follow-up

    Mov. Disord.

    (2001)
  • G. Alves et al.

    Is fatigue an independent and persistent symptom in patients with Parkinson disease?

    Neurology

    (2004)
  • V.B. Dogan et al.

    Independent effect of fatigue on health-related quality of life in patients with idiopathic Parkinson's disease

    Neurol. Sci.

    (2015)
  • L.A. Uebelacker et al.

    A survey of Parkinson's disease patients: most bothersome symptoms and coping preferences

    J. Parasit. Dis.

    (2014)
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