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

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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.

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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.

Author information

Authors and Affiliations

  1. Department for Parkinson’s Disease, IRCCS San Camillo, Via Alberoni 70, Venice, Italy

    Angelo Antonini

  2. Centro Parkinson, Istituti Clinici di Perfezionamento, Milan, Italy

    Angelo Antonini

  3. Dipartimento Scienze Neurologiche, Scuola Medica Salernitana, Centro Parkinson, Università di Salerno, Salerno, Italy

    Paolo Barone

  4. IDC-Hermitage-Capodimonte, Naples, Italy

    Paolo Barone

  5. Ospedale della Misericordia, Grosseto, Italy

    Roberto Marconi

  6. Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Università di Messina, Messina, Italy

    Letterio Morgante

  7. Ospedale Umberto I, Enna, Italy

    Salvatore Zappulla

  8. Ospedale Sant’Andrea, II Facoltà di Medicina e Chirurgia, “Sapienza” Università di Roma, Rome, Italy

    Francesco Ernesto Pontieri

  9. Dip. Scienze Neurologiche e Psichiatriche, Day Hospital, Florence, Italy

    Silvia Ramat

  10. Ospedale Umberto I, Ancona, Italy

    Maria Gabriella Ceravolo

  11. Dipartimento di Neurologia e Psichiatria e Centro di Ricerca per le Malattie Sociali (CIMS), Centro Parkinson, “Sapienza” Università di Roma, Rome, Italy

    Giuseppe Meco

  12. A.O.R.N. San Giuseppe Moscati, Avellino, Italy

    Giulio Cicarelli

  13. Ospedale Civile, Vimercate, Italy

    Massimo Pederzoli

  14. Fondazione Poliambulanza, Brescia, Italy

    Michela Manfredi

  15. Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Roberto Ceravolo

  16. Policlinico Universitario Udine, Udine, Italy

    Marco Mucchiut

  17. Presidio Ospedaliero S. Luca, Vallo della Lucania, Italy

    Giampiero Volpe

  18. Università degli Studi di Genova, Genoa, Italy

    Giovanni Abbruzzese

  19. Ospedale Regionale, Aosta, Italy

    Edo Bottacchi

  20. Ospedale Civile San Bortolo, Vicenza, Italy

    Luigi Bartolomei

  21. Policlinico Le Scotte, Siena, Italy

    Giuseppe Ciacci

  22. Policlinico Universitario di Monserrato, Monserrato, Italy

    Antonino Cannas

  23. Azienda Ospedaliera S. Elia, Caltanissetta, Italy

    Maria Giovanna Randisi

  24. Presidio Ospedaliero Annunziata, Cosenza, Italy

    Alfredo Petrone

  25. Ospedale Ramazzini, Carpi, Italy

    Mario Baratti

  26. P.O. F. Ferrari, Casarano, Italy

    Vincenzo Toni

  27. Azienda Ospedaliera G. Brotzu, Cagliari, Italy

    Giovanni Cossu

  28. Ospedale Versilia, Camajore, Italy

    Paolo Del Dotto

  29. Università Cattolica S. Cuore Policlinico Gemelli, Rome, Italy

    Anna Rita Bentivoglio

  30. Ospedale di Marsala ASP TP/2, Marsala, Italy

    Michele Abrignani

  31. Ospedale S. Maria Loreto Nuovo, Naples, Italy

    Rossana Scala

  32. Ospedale di Castelvetrano, Castelvetrano, Italy

    Franco Pennisi

  33. Ospedale Sant’Anna, Ferrara, Italy

    Rocco Quatrale

  34. Ospedale dell’Angelo ULS12 Veneziana, Mestre, Italy

    Rocco Quatrale

  35. Az. Osp. S.Giovanni di Dio, Agrigento, Italy

    Rosa Maria Gaglio

  36. Policlinico Universitario, Catania, Italy

    Alessandra Nicoletti

  37. Ospedale S. Antonio Abate Gallarate, Gallarate, Italy

    Michele Perini

  38. O.R. Villa Sofia, Palermo, Italy

    Tania Avarello

  39. Università di Roma Tor Vergata, Rome, Italy

    Antonio Pisani

  40. Ospedale di Vaio, Fidenza, Italy

    Augusto Scaglioni

  41. Dipartimento Scienze Neurologiche, Università di Bologna, Bologna, Italy

    Paolo Emilio Martinelli

  42. P.O. Guzzardi, Vittoria, Italy

    Francesco Iemolo

  43. Ospedale Cattinara, Trieste, Italy

    Laura Ferigo

  44. Azienda Ospedaliero Universitaria Integrata Verona, Verona, Italy

    Laura Ferigo

  45. Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

    Pasqualino Simone

  46. Istituto Nazionale Neurologico C. Besta, Milan, Italy

    Paola Soliveri

  47. Istituto Clinico Città di Brescia, Brescia, Italy

    Biagio Troianiello

  48. Ospedale G. Iazzolino, Vibo Valentia, Italy

    Domenico Consoli

  49. Istituto Scientifico San Giuseppe, Piancavallo, Italy

    Alessandro Mauro

  50. Università degli Studi di Torino, Turin, Italy

    Leonardo Lopiano

  51. Az. Osp. Papardo, Messina, Italy

    Giuseppe Nastasi

  52. Policlinico Umberto I, Univ. La Sapienza, Rome, Italy

    Carlo Colosimo

Authors
  1. Angelo Antonini
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  2. Paolo Barone
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  3. Roberto Marconi
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  4. Letterio Morgante
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  5. Salvatore Zappulla
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  6. Francesco Ernesto Pontieri
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  7. Silvia Ramat
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  8. Maria Gabriella Ceravolo
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  9. Giuseppe Meco
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  10. Giulio Cicarelli
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  11. Massimo Pederzoli
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  12. Michela Manfredi
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  13. Roberto Ceravolo
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  14. Marco Mucchiut
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  15. Giampiero Volpe
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  16. Giovanni Abbruzzese
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  17. Edo Bottacchi
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  18. Luigi Bartolomei
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  19. Giuseppe Ciacci
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  20. Antonino Cannas
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  21. Maria Giovanna Randisi
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  22. Alfredo Petrone
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  23. Mario Baratti
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  24. Vincenzo Toni
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  25. Giovanni Cossu
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  26. Paolo Del Dotto
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  27. Anna Rita Bentivoglio
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  28. Michele Abrignani
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  29. Rossana Scala
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  30. Franco Pennisi
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  31. Rocco Quatrale
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  32. Rosa Maria Gaglio
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  33. Alessandra Nicoletti
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  34. Michele Perini
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  35. Tania Avarello
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  36. Antonio Pisani
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  37. Augusto Scaglioni
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  38. Paolo Emilio Martinelli
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  39. Francesco Iemolo
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  40. Laura Ferigo
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  41. Pasqualino Simone
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  42. Paola Soliveri
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  43. Biagio Troianiello
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  44. Domenico Consoli
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  45. Alessandro Mauro
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  46. Leonardo Lopiano
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  47. Giuseppe Nastasi
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  48. Carlo Colosimo
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Corresponding author

Correspondence to Angelo Antonini.

Additional information

On behalf of the PRIAMO study group.

The members of the PRIAMO study group are given in Appendix 1.

Appendices

Appendix 1: The PRIAMO study group

First name

Last name

Unit

Hospital

Town

Salvatore

Zappulla

Neurologia

Ospedale Umberto I

Enna

Clelia

Pellicano

Clinica Neurologica

Ospedale Sant’Andrea, II Facoltà di Medicina e Chirurgia, “Sapienza” Università di Roma

Roma

Sara

Meoni

Clinica Neurologica I

Day Hospital Dip. Scienze Neurologiche e Psichiatriche

Firenze

Marianna

Capecci

Clinica di Neuroriabilitazione

Ospedale Umberto I

Ancona

Natalia

Caravona

Centro Parkinson Dipartimento di Neurologia e Psichiatria e Centro di Ricerca per le Malattie Sociali (CIMS)

“Sapienza” Università di Roma

Roma

Gianni

Pezzoli

Centro Parkinson

Istituti Clinici di Perfezionamento

Milano

Vittorio

Petretta

Neurologia e Stroke

A.O.R.N. San Giuseppe Moscati

Avellino

Massimo

Pederzoli

Neurologia

Ospedale Civile

Vimercate

Fulvio

Pepe

Neurologia

Fondazione Poliambulanza

Brescia

Marianna

Amboni

 

IDC-Hermitage-Capodimonte

Napoli

Daniela

Frosini

Centro Parkinson

Azienda Ospedaliero-Universitaria Pisana

Pisa

Sergio

Zanini

Clinica Neurologica

Policlinico Universitario Udine

Udine

Giampiero

Volpe

Neurofisiopatologia Dip. Neuro Orto Traumatologia

Presidio Ospedaliero S. Luca

Vallo della Lucania

Gilda

Di Brigida

Dipartimento Neuroscienze, Oftalmologia e Genetica

Università degli Studi di Genova

Genova

Marco

Di Giovanni

U.O. di Neurologia

Ospedale Regionale

Aosta

Roberto

L’Erario

Neurologia

Ospedale Civile San Bortolo

Vicenza

Giuseppe

Ciacci

Neurologia

Policlinico Le Scotte

Siena

Antonio

Cannas

U.O.Neurologia

Policlinico Universitario di Monserrato

Monserrato, Cagliari

Luisa

Giglia

Neurologia

Azienda Ospedaliera S. Elia

Caltanissetta

Alfredo

Petrone

Neurologia

Presidio Ospedaliero Annunziata

Cosenza

Stefano

Amidei

Neurologia

Ospedale Ramazzini

Carpi

Giorgio

Trianni

Neurologia

P.O. F. Ferrari

Casarano

Giovanni

Cossu

Centro Parkinson -U.O.Neurologia

Azienda Ospedaliera G.BROTZU

Cagliari

Maria

Bloise

Dip.to Scienze Neurologiche

Policlinico Umberto I Univ.La Sapienza

Roma

Chiara

Logi

U.O Neurologia

Ospedale Versilia

Camajore

Francesco

Soleti

Clinica Neurologica

Università Cattolica S. Cuore Policlinico Gemelli

Roma

Michele

Abrignani

U.O. Neurologia

Ospedale di Marsala ASP TP/2

Marsala

Rossana

Scala

Neurologia

Ospedale S. Maria Loreto Nuovo

Napoli

Franco

Pennisi

Neurologia

Ospedale di Castelvetrano

Castelvetrano

Lucia

Grasso

Neurologia

Ospedale della Misericordia

Grosseto

Francesca

Preda

Neurologia Dip. Neuroscienze applicate alla clinica

Ospedale Sant’Anna

Ferrara

Giacomo

Gurgone

U.O. Neurologia

Az. Osp. S.Giovanni di Dio

Agrigento

Mario

Zappia

Clinica Neurologica I

Policlinico Universitario

Catania

Stefania

Lanfranchi

Neurologia

Ospedale S. Antonio Abate Gallarate

Gallarate

Tania

Avarello

Centro per lo studio delle M.Extrapiramidali

O.R. Villa Sofia

Palermo

Francesca

Morgante

Dipartimento di Neuroscienze, Scienze psichiatriche ed Anestesiologiche

Università di Messina

Messina

Paolo

Stanzione

Dept. Neuroscience

Università di Roma Tor Vergata

Roma

Augusto

Scaglioni

Div. Neurologia

Ospedale di Vaio

Fidenza

Sabina

Capellari

Centro per lo studio e la cura delle malattie extrapiramidali

Dipartimento Scienze Neurologiche Università di Bologna

Bologna

Monia

Blundo

U.O. Neurologia

P.O. Guzzardi

Vittoria

Lucia

Antonutti

Clinica Neurologica

Ospedale di Cattinara

Trieste

Pasqualino

Simone

Neurologia

Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo

Paola

Soliveri

Neurologia I

Istituto Nazionale Neurologico C. Besta

Milano

Biagio

Troianello

Neurologia

Istituto Clinico Città di Brescia

Brescia

Mattia Anna

Iellamo

U.O. Neurologia

Ospedale G. Iazzolino

Vibo Valentia

Alessandro

Mauro

Neurologia

Istituto Scientifico San Giuseppe

Piancavallo

Maurizio

Zibetti

Dipartimento Neuroscienze

Università degli Studi di Torino

Torino

Giuseppe

Nastasi

Neurologia

Az. Osp. Papardo

Messina

Appendix 2

Steering committee

Angelo Antonini:

Department for Parkinson’s disease IRCCS San Camillo, Venezia

Paolo Barone:

Scuola Medica Salernitana, Università di Salerno, Salerno; IDC-Hermitage-Capodimonte, Napoli

Carlo Colosimo:

Università La Sapienza, Roma

Roberto Marconi:

Ospedale della Misericordia, Grosseto

Letterio Morgante:

Dipartimento di Neuroscienze, Scienze Psichiatriche ed Anestesiologiche, Università di Messina, Italy.

Sponsorship

  • Tania Corbetta, Arina Dumitriu, Boehringer Ingelheim, Milan, Italy.

Project management, statistical analyses, and data management

  • Simona Sgarbi, project leader MediData Studi e Ricerche, Modena

  • Andrea Rapisarda, clinical project manager MediData Studi e Ricerche, Modena

  • Sara Rizzoli, Lucia Simoni, statisticians MediData Studi e Ricerche, Modena

  • Luca Zanoli, clinical data manager MediData Studi e Ricerche, Modena

  • Alessandra Manfredi, clinical operation specialist MediData Studi e Ricerche, Modena, Italy.

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Antonini, A., Barone, P., Marconi, R. et al. The progression of non-motor symptoms in Parkinson’s disease and their contribution to motor disability and quality of life. J Neurol 259, 2621–2631 (2012). https://doi.org/10.1007/s00415-012-6557-8

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  • DOI: https://doi.org/10.1007/s00415-012-6557-8

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