title: Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease.
abstract: BACKGROUND
  Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.
  
  
  OBJECTIVE
  To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.
  
  
  METHODS
  The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.
  
  
  RESULTS
  University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination.
  
  
  CONCLUSIONS
  Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD.
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Gaig
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Vilas
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Neurology Service, Hospital Universitario Marqués de Valdecilla, University of Cantabria (UC), Santander, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Neurology Service, Hospital Universitario Marqués de Valdecilla, University of Cantabria (UC), Santander, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sierra
authors.affiliation: Neurology Service, Hospital de Galdakao, Usansolo, Vizcaya, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: García-Gorostiaga
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Buongiorno
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Ezquerra
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Martí
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Valldeoriola
authors.affiliation: Neurology Service, Hospital Universitari Mutua de Terrasa, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Aguilar
authors.affiliation: Neurology Service, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Calopa
authors.affiliation: Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Hernandez-Vara
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003248:Constipation / Q000150:complications / Q000175:diagnosis*; D003863:Depression / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D000857:Olfaction Disorders / Q000150:complications / Q000175:diagnosis*; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012737:Sex Factors; D012893:Sleep Wake Disorders / Q000150:complications / Q000175:diagnosis*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases