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Journal of Neurology

, Volume 259, Issue 12, pp 2621–2631 | Cite as

The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life

  • Angelo AntoniniEmail author
  • Paolo Barone
  • Roberto Marconi
  • Letterio Morgante
  • Salvatore Zappulla
  • Francesco Ernesto Pontieri
  • Silvia Ramat
  • Maria Gabriella Ceravolo
  • Giuseppe Meco
  • Giulio Cicarelli
  • Massimo Pederzoli
  • Michela Manfredi
  • Roberto Ceravolo
  • Marco Mucchiut
  • Giampiero Volpe
  • Giovanni Abbruzzese
  • Edo Bottacchi
  • Luigi Bartolomei
  • Giuseppe Ciacci
  • Antonino Cannas
  • Maria Giovanna Randisi
  • Alfredo Petrone
  • Mario Baratti
  • Vincenzo Toni
  • Giovanni Cossu
  • Paolo Del Dotto
  • Anna Rita Bentivoglio
  • Michele Abrignani
  • Rossana Scala
  • Franco Pennisi
  • Rocco Quatrale
  • Rosa Maria Gaglio
  • Alessandra Nicoletti
  • Michele Perini
  • Tania Avarello
  • Antonio Pisani
  • Augusto Scaglioni
  • Paolo Emilio Martinelli
  • Francesco Iemolo
  • Laura Ferigo
  • Pasqualino Simone
  • Paola Soliveri
  • Biagio Troianiello
  • Domenico Consoli
  • Alessandro Mauro
  • Leonardo Lopiano
  • Giuseppe Nastasi
  • Carlo Colosimo
Original Communication

Abstract

Non-motor symptoms are gaining relevance in Parkinson’s disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1–10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (H&Y) stage was used to categorize patient status (I–II mild; III moderate; IV–V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening (p < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months (p < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones (p < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.

Keywords

Parkinson’s disease Non-motor symptoms Mortality Cognition Quality of life Motor progression 

Notes

Conflicts of interest

A. Antonini has received honoraria for consulting services and symposia from Abbott, Boehringer Ingelheim, GSK, Lundbeck, UCB, Novartis and Merck Serono; P. Barone has received honoraria for consulting services and symposia from Boehringer Ingelheim; R. Marconi has received honoraria for consulting services and symposia from Boehringer Ingelheim; L. Morgante has received honoraria for consulting services and symposia from Boehringer Ingelheim; C. Colosimo has received honoraria for consulting services and symposia from Boehringer Ingelheim; and all other authors have nothing to disclose.

Ethical standards

The study was approved by the Ethic Committee of each individual institution.

References

  1. 1.
    Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21:916–923PubMedCrossRefGoogle Scholar
  2. 2.
    Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P, Macphee G et al (2007) Prevalence of nonmotor symptoms in Parkinson’s disease in an international setting; study using nonmotor symptoms questionnaire in 545 patients. Mov Disord 22:1623–1629PubMedCrossRefGoogle Scholar
  3. 3.
    Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E et al (2009) The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649PubMedCrossRefGoogle Scholar
  4. 4.
    Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P et al (2007) The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 22:1901–1911PubMedCrossRefGoogle Scholar
  5. 5.
    Simuni T, Sethi K (2008) Non-motor manifestations of Parkinson’s disease. Ann Neurol 64(Suppl 2):S65–S80PubMedGoogle Scholar
  6. 6.
    Beiske AG, Loge JH, Rønningen A, Svensson E (2009) Pain in Parkinson’s disease: prevalence and characteristics. Pain 141:173–177PubMedCrossRefGoogle Scholar
  7. 7.
    Honig H, Antonini A, Martinez-Martin P, Forgacs I, Faye GC, Fox T et al (2009) Intrajejunal levodopa infusion in Parkinson’s disease: a pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov Disord 24:1468–1474PubMedCrossRefGoogle Scholar
  8. 8.
    Barone P, Poewe W, Albrecht S et al (2010) Pramipexole for the treatment of depressive symptoms in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 9:573–580PubMedCrossRefGoogle Scholar
  9. 9.
    Hely MA, Morris JG, Reid WG, Trafficante R (2005) Sydney Multicenter Study of Parkinson’s disease: non-L-dopa responsive problems dominate at 15 years. Mov Disord 20:190–199PubMedCrossRefGoogle Scholar
  10. 10.
    Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D (2008) Dementia and survival in Parkinson disease: a 12-year population study. Neurology 70:1017–1022PubMedCrossRefGoogle Scholar
  11. 11.
    Chaudhuri KR, Schapira AH (2009) Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 8(5):464–474PubMedCrossRefGoogle Scholar
  12. 12.
    Antonini A, Colosimo C, Marconi R, Morgante L, Barone P (2008) The PRIAMO Study: background, methods and recruitment. Neurol Sci 29:61–65PubMedCrossRefGoogle Scholar
  13. 13.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedCrossRefGoogle Scholar
  14. 14.
    Fahn S, Elton R, Members of the UPDRS Development Committee (1987) The unified Parkinson’s disease rating scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M (eds) Recent developments in Parkinson’s disease, vol 2. Macmillan Health Care Information, Florham Park, pp 153–63, 293–304Google Scholar
  15. 15.
    Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198PubMedCrossRefGoogle Scholar
  16. 16.
    Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a Frontal Assessment Battery at bedside. Neurology 55:1621–1626PubMedCrossRefGoogle Scholar
  17. 17.
    Peto V, Jenkinson C, Fitzpatrick R, Greenhall R (1995) The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 4:241–248PubMedCrossRefGoogle Scholar
  18. 18.
    Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62PubMedCrossRefGoogle Scholar
  19. 19.
    McDowell I, Newell C (1996) Measuring health: a guide to rating scales and questionnaires. Oxford University Press, New YorkGoogle Scholar
  20. 20.
    Measso GF, Cavarzeran F, Zappalà G, Lebowitz BD, Pirozzolo FJ, Amaducci LA et al (1993) The Mini-Mental State Examination: normative study of a random sample of Italian population. Dev Neuropsychol 9:77–85CrossRefGoogle Scholar
  21. 21.
    Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, Villa ML et al (2005) The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci 26:108–116PubMedCrossRefGoogle Scholar
  22. 22.
    Istituto Nazionale di Statistica (2008) Tavole di mortalità della popolazione residenteGoogle Scholar
  23. 23.
    Poewe W, Mahlknecht P (2009) The clinical progression of Parkinson’s disease. Parkinsonism Relat Disord 15:S28–S32PubMedCrossRefGoogle Scholar
  24. 24.
    Schrag A, Dodel R, Spottke A, Bornschein B, Siebert U, Quinn NP (2007) Rate of clinical progression in Parkinson’s disease. A prospective study. Mov Disord 22:938–945PubMedCrossRefGoogle Scholar
  25. 25.
    Maetzler W, Liepelt I, Liepelt I, Berg D (2009) Progression of Parkinson’s disease in the clinical phase: potential markers. Lancet Neurol 8:1158–1171PubMedCrossRefGoogle Scholar
  26. 26.
    Chaudhuri KR, Prieto-Jurcynska C, Naidu Y, Mitra T, Frades-Payo B, Tluk S et al (2010) The non-declaration of nonmotor symptoms of Parkinson’s disease to health care professionals: an international study using the nonmotor symptoms questionnaire. Mov Disord 25:697–701CrossRefGoogle Scholar
  27. 27.
    Trenkwalder C, Kies B, Rudzinska M et al (2011) Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: a double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 26(1):90–99PubMedCrossRefGoogle Scholar
  28. 28.
    Hoops S, Nazem S, Siderowf AD et al (2009) Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 73(21):1738–1745PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Angelo Antonini
    • 1
    • 2
    Email author
  • Paolo Barone
    • 3
    • 4
  • Roberto Marconi
    • 5
  • Letterio Morgante
    • 6
  • Salvatore Zappulla
    • 7
  • Francesco Ernesto Pontieri
    • 8
  • Silvia Ramat
    • 9
  • Maria Gabriella Ceravolo
    • 10
  • Giuseppe Meco
    • 11
  • Giulio Cicarelli
    • 12
  • Massimo Pederzoli
    • 13
  • Michela Manfredi
    • 14
  • Roberto Ceravolo
    • 15
  • Marco Mucchiut
    • 16
  • Giampiero Volpe
    • 17
  • Giovanni Abbruzzese
    • 18
  • Edo Bottacchi
    • 19
  • Luigi Bartolomei
    • 20
  • Giuseppe Ciacci
    • 21
  • Antonino Cannas
    • 22
  • Maria Giovanna Randisi
    • 23
  • Alfredo Petrone
    • 24
  • Mario Baratti
    • 25
  • Vincenzo Toni
    • 26
  • Giovanni Cossu
    • 27
  • Paolo Del Dotto
    • 28
  • Anna Rita Bentivoglio
    • 29
  • Michele Abrignani
    • 30
  • Rossana Scala
    • 31
  • Franco Pennisi
    • 32
  • Rocco Quatrale
    • 33
    • 34
  • Rosa Maria Gaglio
    • 35
  • Alessandra Nicoletti
    • 36
  • Michele Perini
    • 37
  • Tania Avarello
    • 38
  • Antonio Pisani
    • 39
  • Augusto Scaglioni
    • 40
  • Paolo Emilio Martinelli
    • 41
  • Francesco Iemolo
    • 42
  • Laura Ferigo
    • 43
    • 44
  • Pasqualino Simone
    • 45
  • Paola Soliveri
    • 46
  • Biagio Troianiello
    • 47
  • Domenico Consoli
    • 48
  • Alessandro Mauro
    • 49
  • Leonardo Lopiano
    • 50
  • Giuseppe Nastasi
    • 51
  • Carlo Colosimo
    • 52
  1. 1.Department for Parkinson’s DiseaseIRCCS San CamilloVeniceItaly
  2. 2.Centro ParkinsonIstituti Clinici di PerfezionamentoMilanItaly
  3. 3.Dipartimento Scienze Neurologiche, Scuola Medica Salernitana, Centro ParkinsonUniversità di SalernoSalernoItaly
  4. 4.IDC-Hermitage-CapodimonteNaplesItaly
  5. 5.Ospedale della MisericordiaGrossetoItaly
  6. 6.Dipartimento di Neuroscienze, Scienze Psichiatriche ed AnestesiologicheUniversità di MessinaMessinaItaly
  7. 7.Ospedale Umberto IEnnaItaly
  8. 8.Ospedale Sant’Andrea, II Facoltà di Medicina e Chirurgia“Sapienza” Università di RomaRomeItaly
  9. 9.Dip. Scienze Neurologiche e PsichiatricheDay HospitalFlorenceItaly
  10. 10.Ospedale Umberto IAnconaItaly
  11. 11.Dipartimento di Neurologia e Psichiatria e Centro di Ricerca per le Malattie Sociali (CIMS), Centro Parkinson“Sapienza” Università di RomaRomeItaly
  12. 12.A.O.R.N. San Giuseppe MoscatiAvellinoItaly
  13. 13.Ospedale CivileVimercateItaly
  14. 14.Fondazione PoliambulanzaBresciaItaly
  15. 15.Azienda Ospedaliero-Universitaria PisanaPisaItaly
  16. 16.Policlinico Universitario UdineUdineItaly
  17. 17.Presidio Ospedaliero S. LucaVallo della LucaniaItaly
  18. 18.Università degli Studi di GenovaGenoaItaly
  19. 19.Ospedale RegionaleAostaItaly
  20. 20.Ospedale Civile San BortoloVicenzaItaly
  21. 21.Policlinico Le ScotteSienaItaly
  22. 22.Policlinico Universitario di MonserratoMonserratoItaly
  23. 23.Azienda Ospedaliera S. EliaCaltanissettaItaly
  24. 24.Presidio Ospedaliero AnnunziataCosenzaItaly
  25. 25.Ospedale RamazziniCarpiItaly
  26. 26.P.O. F. FerrariCasaranoItaly
  27. 27.Azienda Ospedaliera G. BrotzuCagliariItaly
  28. 28.Ospedale VersiliaCamajoreItaly
  29. 29.Università Cattolica S. Cuore Policlinico GemelliRomeItaly
  30. 30.Ospedale di Marsala ASP TP/2MarsalaItaly
  31. 31.Ospedale S. Maria Loreto NuovoNaplesItaly
  32. 32.Ospedale di CastelvetranoCastelvetranoItaly
  33. 33.Ospedale Sant’AnnaFerraraItaly
  34. 34.Ospedale dell’Angelo ULS12 VenezianaMestreItaly
  35. 35.Az. Osp. S.Giovanni di DioAgrigentoItaly
  36. 36.Policlinico UniversitarioCataniaItaly
  37. 37.Ospedale S. Antonio Abate GallarateGallarateItaly
  38. 38.O.R. Villa SofiaPalermoItaly
  39. 39.Università di Roma Tor VergataRomeItaly
  40. 40.Ospedale di VaioFidenzaItaly
  41. 41.Dipartimento Scienze NeurologicheUniversità di BolognaBolognaItaly
  42. 42.P.O. GuzzardiVittoriaItaly
  43. 43.Ospedale CattinaraTriesteItaly
  44. 44.Azienda Ospedaliero Universitaria Integrata VeronaVeronaItaly
  45. 45.Ospedale Casa Sollievo della SofferenzaSan Giovanni RotondoItaly
  46. 46.Istituto Nazionale Neurologico C. BestaMilanItaly
  47. 47.Istituto Clinico Città di BresciaBresciaItaly
  48. 48.Ospedale G. IazzolinoVibo ValentiaItaly
  49. 49.Istituto Scientifico San GiuseppePiancavalloItaly
  50. 50.Università degli Studi di TorinoTurinItaly
  51. 51.Az. Osp. PapardoMessinaItaly
  52. 52.Policlinico Umberto IUniv. La SapienzaRomeItaly

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