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Fatigue in Parkinson's disease

Published:December 28, 2016DOI:https://doi.org/10.1016/j.jns.2016.12.061

      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.

      Keywords

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      References

        • Friedman J.H.
        • Beck J.C.
        • Chou K.L.
        • Clark G.
        • Fagundes C.P.
        • Goetz C.G.
        • Herlofson K.
        • Kluger B.
        • Krupp L.B.
        • Lang A.E.
        • Lou J.S.
        • Marsh L.
        • Newbould A.
        • Weintraub D.
        Fatigue in Parkinson's Disease: Report From a Mutidisciplinary Symposium, NPJ Parkinson's Disease 2.
        2016
        • Pont-Sunyer C.
        • Hotter A.
        • Gaig C.
        • Seppi K.
        • Compta Y.
        • Katzenschlager R.
        • Mas N.
        • Hofeneder D.
        • Brucke T.
        • Bayes A.
        • Wenzel K.
        • Infante J.
        • Zach H.
        • Pirker W.
        • Posada I.J.
        • Alvarez R.
        • Ispierto L.
        • De Fabregues O.
        • Callen A.
        • Palasi A.
        • Aguilar M.
        • Marti M.J.
        • Valldeoriola F.
        • Salamero M.
        • Poewe W.
        • Tolosa E.
        The onset of nonmotor symptoms in Parkinson's disease (The ONSET PD Study).
        Mov. Disord. 2014;
        • Hoehn M.M.
        • Yahr M.D.
        Parkinsonism: onset, progression and mortality.
        Neurology. 1967; 17: 427-442
        • Friedman J.
        • Friedman H.
        Fatigue in Parkinson's disease.
        Neurology. 1993; 43: 2016-2018
        • van Hilten J.J.
        • Weggeman M.
        • der Velde van
        • Kerkhof G.A.
        • van Dijk J.G.
        • Roos R.A.
        Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease.
        J. Neural Transm. Park. Dis. Dement. Sect. 1993; 5 (1993): 235-244
        • Karlsen K.
        • Larsen J.P.
        • Tandberg E.
        • Jorgensen K.
        Fatigue in patients with Parkinson's disease.
        Mov. Disord. 1999; 14: 237-241
        • Abe K.
        • Takanashi M.
        • Yanagihara T.
        Fatigue in patients with Parkinson's disease.
        Behav. Neurol. 2000; 12: 103-106
        • Shulman L.M.
        • Taback R.L.
        • Bean J.
        • Weiner W.J.
        Comorbidity of the nonmotor symptoms of Parkinson's disease.
        Mov. Disord. 2001; 16: 507-510
        • Schenkman M.
        • Wei Zhu C.
        • Cutson T.M.
        • Whetten-Goldstein K.
        Longitudinal evaluation of economic and physical impact of Parkinson's disease.
        Parkinsonism Relat. Disord. 2001; 8: 41-50
        • Herlofson K.
        • Larsen J.P.
        Measuring fatigue in patients with Parkinson's disease - the Fatigue Severity Scale.
        Eur. J. Neurol. 2002; 9: 595-600
        • Schifitto G.
        • Friedman J.H.
        • Oakes D.
        • Shulman L.
        • Comella C.L.
        • Marek K.
        • Fahn S.
        Fatigue in levodopa-naive subjects with Parkinson disease.
        Neurology. 2008; 71: 481-485
        • Barone P.
        • Antonini A.
        • Colosimo C.
        • Marconi R.
        • Morgante L.
        • Avarello T.P.
        • Bottacchi E.
        • Cannas A.
        • Ceravolo G.
        • Ceravolo R.
        • Cicarelli G.
        • Gaglio R.M.
        • Giglia R.M.
        • Iemolo F.
        • Manfredi M.
        • Meco G.
        • Nicoletti A.
        • Pederzoli M.
        • Petrone A.
        • Pisani A.
        • Pontieri F.E.
        • Quatrale R.
        • Ramat S.
        • Scala R.
        • Volpe G.
        • Zappulla S.
        • Bentivoglio A.R.
        • Stocchi F.
        • Trianni G.
        • Dotto P.D.
        The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.
        Mov. Disord. 2009; 24: 1641-1649
        • Goulart F.O.
        • Godke B.A.
        • Borges V.
        • Azevedo-Silva S.M.
        • Mendes M.F.
        • Cendoroglo M.S.
        • Ferraz H.B.
        Fatigue in a cohort of geriatric patients with and without Parkinson's disease.
        Braz. J. Med. Biol. Res. 2009; 42: 771-775
        • Gallagher D.A.
        • Lees A.J.
        • Schrag A.
        What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them?.
        Mov. Disord. 2010; 25: 2493-2500
        • Beiske A.G.
        • Loge J.H.
        • Hjermstad M.J.
        • Svensson E.
        Fatigue in Parkinson's disease: prevalence and associated factors.
        Mov. Disord. 2010; 25: 2456-2460
        • Martinez-Martin P.
        • Rodriguez-Blazquez C.
        • Kurtis M.M.
        • Chaudhuri K.R.
        The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease.
        Mov. Disord. 2011; 26: 399-406
        • Miwa H.
        • Miwa T.
        Fatigue in patients with Parkinson's disease: impact on quality of life.
        Intern. Med. 2011; 50: 1553-1558
        • Herlofson K.
        • Ongre S.O.
        • Enger L.K.
        • Tysnes O.B.
        • Larsen J.P.
        Fatigue in early Parkinson's disease. Minor inconvenience or major distress?.
        Eur. J. Neurol. 2012; 19: 963-968
        • Friedman J.H.
        • Friedman H.
        Fatigue in Parkinson's disease: a nine-year follow-up.
        Mov. Disord. 2001; 16: 1120-1122
        • Alves G.
        • Wentzel-Larsen T.
        • Larsen J.P.
        Is fatigue an independent and persistent symptom in patients with Parkinson disease?.
        Neurology. 2004; 63: 1908-1911
        • Muller B.
        • Assmus J.
        • Herlofson K.
        • Larsen J.P.
        • Tysnes O.B.
        Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease.
        Parkinsonism Relat. Disord. 2013; 19: 1027-1032
        • Pfeiffer R.F.
        Non-motor symptoms in Parkinson's disease.
        Parkinsonism Relat. Disord. 2016; 22: S119-S122
        • Martinez-Martin P.
        The importance of non-motor disturbances to quality of life in Parkinson's disease.
        J. Neurol. Sci. 2011; 310: 12-16
        • Dogan V.B.
        • Koksal A.
        • Dirican A.
        • Baybas S.
        • Dirican A.
        • Dogan G.B.
        Independent effect of fatigue on health-related quality of life in patients with idiopathic Parkinson's disease.
        Neurol. Sci. 2015; 36: 2221-2226
        • Song W.
        • Guo X.
        • Chen K.
        • Chen X.
        • Cao B.
        • Wei Q.
        • Huang R.
        • Zhao B.
        • Wu Y.
        • Shang H.F.
        The impact of non-motor symptoms on the health-related quality of life of Parkinson's disease patients from Southwest China.
        Parkinsonism Relat. Disord. 2014; 20: 149-152
        • Uebelacker L.A.
        • Epstein-Lubow G.
        • Lewis T.
        • Broughton M.K.
        • Friedman J.H.
        A survey of Parkinson's disease patients: most bothersome symptoms and coping preferences.
        J. Parasit. Dis. 2014; 4: 717-723
        • Zesiewicz T.A.
        • Patel-Larson A.
        • Hauser R.A.
        • Sullivan K.L.
        Social Security Disability Insurance (SSDI) in Parkinson's disease.
        Disabil. Rehabil. 2007; 29: 1934-1936
        • Muscio B.
        Is a fatigue test possible?.
        Br. J. Psychol. 1921; 12: 31-46
        • Kluger B.M.
        • Krupp L.B.
        • Enoka R.M.
        Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy.
        Neurology. 2013; 80: 409-416
        • Kluger B.M.
        • Herlofson K.
        • Chou K.L.
        • Lou J.S.
        • Goetz C.G.
        • Lang A.E.
        • Weintraub D.
        • Friedman J.
        Parkinson's disease-related fatigue: a case definition and recommendations for clinical research.
        Mov. Disord. 2016;
        • Friedman J.H.
        • Alves G.
        • Hagell P.
        • Marinus J.
        • Marsh L.
        • Martinez-Martin P.
        • Goetz C.G.
        • Poewe W.
        • Rascol O.
        • Sampaio C.
        • Stebbins G.
        • Schrag A.
        Fatigue rating scales critique and recommendations by the Movement Disorders Society task force on rating scales for Parkinson's disease.
        Mov. Disord. 2010; 25: 805-822
        • Schiehser D.M.
        • Ayers C.R.
        • Liu L.
        • Lessig S.
        • Song D.S.
        • Filoteo J.V.
        Validation of the Modified Fatigue Impact Scale in Parkinson's disease.
        Parkinsonism Relat. Disord. 2013; 19: 335-338
        • Kos D.
        • Duportail M.
        • D'Hooghe M.
        • Nagels G.
        • Kerckhofs E.
        Multidisciplinary fatigue management programme in multiple sclerosis: a randomized clinical trial.
        Mult. Scler. 2007; 13: 996-1003
        • Lou J.S.
        Physical and mental fatigue in Parkinson's disease: epidemiology, pathophysiology and treatment.
        Drugs Aging. 2009; 26: 195-208
        • Wang C.
        • Ding M.
        • Kluger B.M.
        Change in intraindividual variability over time as a key metric for defining performance-based cognitive fatigability.
        Brain Cogn. 2014; 85: 251-258
        • Pont-Sunyer C.
        • Hotter A.
        • Gaig C.
        • Seppi K.
        • Compta Y.
        • Katzenschlager R.
        • Mas N.
        • Hofeneder D.
        • Brucke T.
        • Bayes A.
        • Wenzel K.
        • Infante J.
        • Zach H.
        • Pirker W.
        • Posada I.J.
        • Alvarez R.
        • Ispierto L.
        • De Fabregues O.
        • Callen A.
        • Palasi A.
        • Aguilar M.
        • Marti M.J.
        • Valldeoriola F.
        • Salamero M.
        • Poewe W.
        • Tolosa E.
        The onset of nonmotor symptoms in Parkinson's disease (the ONSET PD study).
        Mov. Disord. 2015; 30: 229-237
        • Kluger B.M.
        • Parra V.
        • Jacobson C.
        • Garvan C.W.
        • Rodriguez R.L.
        • Fernandez H.H.
        • Fogel A.
        • Skoblar B.M.
        • Bowers D.
        • Okun M.S.
        The prevalence of fatigue following deep brain stimulation surgery in Parkinson's disease and association with quality of life.
        Parkinson's Dis. 2012; 2012: 769506
        • Chou K.L.
        • Persad C.C.
        • Patil P.G.
        Change in fatigue after bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease.
        Parkinsonism Relat. Disord. 2012; 18: 510-513
        • Franssen M.
        • Winward C.
        • Collett J.
        • Wade D.
        • Dawes H.
        Interventions for fatigue in Parkinson's disease: a systematic review and meta-analysis.
        Mov. Disord. 2014; 29: 1675-1678
        • Elbers R.G.
        • Verhoef J.
        • van Wegen E.E.
        • Berendse H.W.
        • Kwakkel G.
        Interventions for fatigue in Parkinson's disease.
        Cochrane Database Syst. Rev. 2015; 10CD010925
        • Friedman J.H.
        • Brown R.G.
        • Comella C.
        • Garber C.E.
        • Krupp L.B.
        • Lou J.S.
        • Marsh L.
        • Nail L.
        • Shulman L.
        • Taylor C.B.
        Fatigue in Parkinson's disease: a review.
        Mov. Disord. 2007; 22: 297-308
        • Stocchi F.
        • Abbruzzese G.
        • Ceravolo R.
        • Cortelli P.
        • D'Amelio M.
        • De Pandis M.F.
        • Fabbrini G.
        • Pacchetti C.
        • Pezzoli G.
        • Tessitore A.
        • Canesi M.
        • Iannacone C.
        • Zappia M.
        Prevalence of fatigue in Parkinson disease and its clinical correlates.
        Neurology. 2014; 83: 215-220
        • van Hilten J.J.
        • Weggeman M.
        • van der Velde E.A.
        • Kerkhof G.A.
        • van Dijk J.G.
        • Roos R.A.
        Sleep, excessive daytime sleepiness and fatigue in Parkinson's disease.
        J. Neural Transm. Park. Dis. Dement. Sect. 1993; 5: 235-244
        • Valko P.O.
        • Waldvogel D.
        • Weller M.
        • Bassetti C.L.
        • Held U.
        • Baumann C.R.
        Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment.
        Eur. J. Neurol. 2010; 17: 1428-1436
        • Chung S.
        • Bohnen N.I.
        • Albin R.L.
        • Frey K.A.
        • Muller M.L.
        • Chervin R.D.
        Insomnia and sleepiness in Parkinson disease: associations with symptoms and comorbidities.
        J. Clin. Sleep Med. 2013; 9: 1131-1137
        • Goldman J.G.
        • Stebbins G.T.
        • Leung V.
        • Tilley B.C.
        • Goetz C.G.
        Relationships among cognitive impairment, sleep, and fatigue in Parkinson's disease using the MDS-UPDRS.
        Parkinsonism Relat. Disord. 2014; 20: 1135-1139
        • Chaudhuri A.
        • Behan P.O.
        Fatigue in neurological disorders.
        Lancet. 2004; 363: 978-988
        • Pavese N.
        • Metta V.
        • Bose S.K.
        • Chaudhuri K.R.
        • Brooks D.J.
        Fatigue in Parkinson's disease is linked to striatal and limbic serotonergic dysfunction.
        Brain. 2010; 133: 3434-3443
        • Chou K.L.
        • Kotagal V.
        • Bohnen N.I.
        Neuroimaging and clinical predictors of fatigue in Parkinson disease.
        Parkinsonism Relat. Disord. 2016; 23: 45-49
        • Capecci M.
        • Petrelli M.
        • Emanuelli B.
        • Millevolte M.
        • Nicolai A.
        • Provinciali L.
        • Ceravolo M.G.
        Rest energy expenditure in Parkinson's disease: role of disease progression and dopaminergic therapy.
        Parkinsonism Relat. Disord. 2013; 19: 238-241
        • Christiansen C.L.
        • Schenkman M.L.
        • McFann K.
        • Wolfe P.
        • Kohrt W.M.
        Walking economy in people with Parkinson's disease.
        Mov. Disord. 2009; 24: 1481-1487
        • Lindqvist D.
        • Kaufman E.
        • Brundin L.
        • Hall S.
        • Surova Y.
        • Hansson O.
        Non-motor symptoms in patients with Parkinson's disease - correlations with inflammatory cytokines in serum.
        PLoS One. 2012; 7e47387
        • Kenangil G.
        • Orken D.N.
        • Ur E.
        • Forta H.
        • Celik M.
        The relation of testosterone levels with fatigue and apathy in Parkinson's disease.
        Clin. Neurol. Neurosurg. 2009; 111: 412-414
        • Lv Z.
        • Qi H.
        • Wang L.
        • Fan X.
        • Han F.
        • Wang H.
        • Bi S.
        Vitamin D status and Parkinson's disease: a systematic review and meta-analysis.
        Neurol. Sci. 2014; 35: 1723-1730
        • Roy S.
        • Sherman A.
        • Monari-Sparks M.J.
        • Schweiker O.
        • Hunter K.
        Correction of low vitamin D improves fatigue: effect of correction of low vitamin D in Fatigue Study (EViDiF Study).
        N. Am. J. Med. Sci. 2014; 6: 396-402
        • Bercea R.M.
        • Mihaescu T.
        • Cojocaru C.
        • Bjorvatn B.
        Fatigue and serum testosterone in obstructive sleep apnea patients.
        Clin. Respir. J. 2015; 9: 342-349
        • Malekzadeh A.
        • Van de Geer-Peeters W.
        • De Groot V.
        • Teunissen C.E.
        • Beckerman H.
        Fatigue in patients with multiple sclerosis: is it related to pro- and anti-inflammatory cytokines?.
        Dis. Markers. 2015; 2015: 758314
        • Santanasto A.J.
        • Glynn N.W.
        • Jubrias S.A.
        • Conley K.E.
        • Boudreau R.M.
        • Amati F.
        • Mackey D.C.
        • Simonsick E.M.
        • Strotmeyer E.S.
        • Coen P.M.
        • Goodpaster B.H.
        • Newman A.B.
        Skeletal muscle mitochondrial function and fatigability in older adults.
        J. Gerontol. A Biol. Sci. Med. Sci. 2015; 70: 1379-1385
        • Richardson C.A.
        • Glynn N.W.
        • Ferrucci L.G.
        • Mackey D.C.
        Walking energetics, fatigability, and fatigue in older adults: the study of energy and aging pilot.
        J. Gerontol. A Biol. Sci. Med. Sci. 2015; 70: 487-494
        • Abe K.
        • Takanashi M.
        • Yanagihara T.
        • Sakoda S.
        Pergolide mesilate may improve fatigue in patients with Parkinson's disease.
        Behav. Neurol. 2001; 13: 117-121
        • Pogarell O.
        • Gasser T.
        • van Hilten J.J.
        • Spieker S.
        • Pollentier S.
        • Meier D.
        • Oertel W.H.
        Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study.
        J. Neurol. Neurosurg. Psychiatry. 2002; 72: 713-720
        • Ongre S.O.
        • Larsen J.P.
        • Tysnes O.B.
        • Herlofson K.
        Fatigue in early Parkinson's disease: the Norwegian ParkWest study.
        Eur. J. Neurol. 2016;
        • Rascol O.
        • Fitzer-Attas C.J.
        • Hauser R.
        • Jankovic J.
        • Lang A.
        • Langston J.W.
        • Melamed E.
        • Poewe W.
        • Stocchi F.
        • Tolosa E.
        • Eyal E.
        • Weiss Y.M.
        • Olanow C.W.
        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; 10: 415-423
        • Lim T.T.
        • Kluger B.M.
        • Rodriguez R.L.
        • Malaty I.A.
        • Palacio Jr., R.
        • Ojo O.O.
        • Patel S.
        • Gujrati Y.
        • Nutter B.
        • Swartz C.
        • Hennessy C.
        • Fernandez H.H.
        Rasagiline for the symptomatic treatment of fatigue in Parkinson's disease.
        Mov. Disord. 2015; 30: 1825-1830
        • Lou J.S.
        • Dimitrova D.M.
        • Park B.S.
        • Johnson S.C.
        • Eaton R.
        • Arnold G.
        • Nutt J.G.
        Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study.
        Clin. Neuropharmacol. 2009; 32: 305-310
        • Mendonca D.A.
        • Menezes K.
        • Jog M.S.
        Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial.
        Mov. Disord. 2007; 22: 2070-2076
        • Tyne H.L.
        • Taylor J.
        • Baker G.A.
        • Steiger M.J.
        Modafinil for Parkinson's disease fatigue.
        J. Neurol. 2010; 257: 452-456
        • Ondo W.G.
        • Fayle R.
        • Atassi F.
        • Jankovic J.
        Modafinil for daytime somnolence in Parkinson's disease: double blind, placebo controlled parallel trial.
        J. Neurol. Neurosurg. Psychiatry. 2005; 76: 1636-1639
        • Rios Romenets S.
        • Creti L.
        • Fichten C.
        • Bailes S.
        • Libman E.
        • Pelletier A.
        • Postuma R.B.
        Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson's disease—a randomized study.
        Parkinsonism Relat. Disord. 2013; 19: 670-675
        • Ondo W.G.
        • Shinawi L.
        • Davidson A.
        • Lai D.
        Memantine for non-motor features of Parkinson's disease: a double-blind placebo controlled exploratory pilot trial.
        Parkinsonism Relat. Disord. 2011; 17: 156-159
        • Canning C.G.
        • Allen N.E.
        • Dean C.M.
        • Goh L.
        • Fung V.S.
        Home-based treadmill training for individuals with Parkinson's disease: a randomized controlled pilot trial.
        Clin. Rehabil. 2012; 26: 817-826
        • Winward C.
        • Sackley C.
        • Meek C.
        • Izadi H.
        • Barker K.
        • Wade D.
        • Dawes H.
        Weekly exercise does not improve fatigue levels in Parkinson's disease.
        Mov. Disord. 2012; 27: 143-146
        • Cugusi L.
        • Solla P.
        • Zedda F.
        • Loi M.
        • Serpe R.
        • Cannas A.
        • Marrosu F.
        • Mercuro G.
        Effects of an adapted physical activity program on motor and non-motor functions and quality of life in patients with Parkinson's disease.
        NeuroRehabilitation. 2014; 35: 789-794
        • Krupp L.B.
        Fatigue in Multiple Sclerosis: A Guide to Diagnosis and Management.
        Demos Medical Publishing Inc., 2004
        • Kluger B.M.
        • Rakowski D.
        • Christian M.
        • Cedar D.
        • Wong B.
        • Crawford J.
        • Uveges K.
        • Berk J.
        • Abaca E.
        • Corbin L.
        • Garvan C.
        Randomized, controlled trial of acupuncture for fatigue in Parkinson's disease.
        Mov. Disord. 2016; 31: 1027-1032
        • Cashion A.K.
        • Gill J.
        • Hawes R.
        • Henderson W.A.
        • Saligan L.
        National Institutes of Health Symptom Science Model sheds light on patient symptoms.
        Nurs. Outlook. 2016; 64: 499-506
        • Tur C.
        Fatigue management in multiple sclerosis.
        Curr. Treat. Options Neurol. 2016; 18: 26