title: The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies.
abstract: Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD.
  
  
  
  To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers.
  
  
  
  A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers.
  
  
  
  G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake.
  
  
  
  G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Neurology Unit, Hospital General de Granollers, Universitat Internacional de Catalunya, Granollers, Spain.
authors.forename: Claustre
authors.initials: C
authors.lastname: Pont-Sunyer
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Caspell-Garcia
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coffey
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Roy N
authors.initials: RN
authors.lastname: Alcalay
authors.affiliation: Departments of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
authors.affiliation: Parkinson's Disease Research, Education and Clinical Center, Michael J. Crescenz VA Medical Center and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.affiliation: The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Facheris
authors.affiliation: Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic of Barcelona, Institutd'InvestigacionsBiomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, and the Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández-Santiago
authors.affiliation: Institute for Neurodegenerative Disorders and Molecular NeuroImaging, New Haven, Connecticut, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Marek
authors.affiliation: Department of Nuclear Medicine, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lomeña
authors.affiliation: Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Connie
authors.initials: C
authors.lastname: Marras
authors.affiliation: Department of Neurology, Movement Disorders Unit. Hospital Universitario Donostia. Biodonostia Research Institute, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), San Sebastián, Guipúzcoa, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Mondragon
authors.affiliation: Department of Neurology, Mount Sinai Beth Israel Medical Center and Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.affiliation: Department of Neurology, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Bjorg
authors.initials: B
authors.lastname: Waro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D003071:Cognition; D003863:Depression / Q000209:etiology / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D054969:Primary Dysautonomias / Q000209:etiology / Q000503:physiopathology; D062706:Prodromal Symptoms; D020187:REM Sleep Behavior Disorder / Q000209:etiology / Q000503:physiopathology; D011795:Surveys and Questionnaires; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: LRRK2 mutations; Parkinson's disease; nonmotor symptoms; prodromal phase