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.
Department for Parkinson's Disease, IRCCS San Camillo, Via Alberoni 70, Venice, Italy. angelo3000@yahoo.com
Angelo
A
Antonini
Paolo
P
Barone
Roberto
R
Marconi
Letterio
L
Morgante
Salvatore
S
Zappulla
Francesco Ernesto
FE
Pontieri
Silvia
S
Ramat
Maria Gabriella
MG
Ceravolo
Giuseppe
G
Meco
Giulio
G
Cicarelli
Massimo
M
Pederzoli
Michela
M
Manfredi
Roberto
R
Ceravolo
Marco
M
Mucchiut
Giampiero
G
Volpe
Giovanni
G
Abbruzzese
Edo
E
Bottacchi
Luigi
L
Bartolomei
Giuseppe
G
Ciacci
Antonino
A
Cannas
Maria Giovanna
MG
Randisi
Alfredo
A
Petrone
Mario
M
Baratti
Vincenzo
V
Toni
Giovanni
G
Cossu
Paolo
P
Del Dotto
Anna Rita
AR
Bentivoglio
Michele
M
Abrignani
Rossana
R
Scala
Franco
F
Pennisi
Rocco
R
Quatrale
Rosa Maria
RM
Gaglio
Alessandra
A
Nicoletti
Michele
M
Perini
Tania
T
Avarello
Antonio
A
Pisani
Augusto
A
Scaglioni
Paolo Emilio
PE
Martinelli
Francesco
F
Iemolo
Laura
L
Ferigo
Pasqualino
P
Simone
Paola
P
Soliveri
Biagio
B
Troianiello
Domenico
D
Consoli
Alessandro
A
Mauro
Leonardo
L
Lopiano
Giuseppe
G
Nastasi
Carlo
C
Colosimo
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019957:Motor Skills Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D010300:Parkinson Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D011446:Prospective Studies; D011788:Quality of Life / Q000523:psychology