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


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



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.


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 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.


  • 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).

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