title: DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G Parkinson's disease.
abstract: BACKGROUND
  The objective of this study was to study motor and nonmotor symptoms and striatal dopaminergic denervation, as well as the relationship between them, in a cohort of asymptomatic relatives of patients with Parkinson's disease (PD) with the R1441G-leucine-rich repeat kinase 2 mutation.
  
  
  METHODS
  Asymptomatic relatives of patients with PD and this mutation were tested for the presence of the mutation and evaluated for striatal, putamenal, and caudate dopaminergic transporters using (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography binding ratios. Clinical and neuropsychological evaluations including timed motor tests, a smell identification test, and global cognition, attention, executive, visuospatial, and memory functions as well as depression, constipation, and rapid eye movement sleep behavior disorder were also assessed.
  
  
  RESULTS
  Twenty-seven carriers and 19 noncarriers were studied. Compared with noncarriers, mutation carriers had significantly lower (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan mean striatal (P = 0.03), mean putamenal (P = 0.01), and lowest putamenal (P = 0.01) binding ratios. Multiple linear regression analysis showed that the carrier status and the execution of timed tests significantly predicted striatal (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane binding. The proportion of variation accounted for by the regression model of these variables was 69% for the putamen and 53% for the caudate nucleus.
  
  
  CONCLUSIONS
  Asymptomatic carriers of the R1441G-leucine-rich repeat kinase 2 mutation have evidence of dopaminergic nigrostriatal denervation, mainly in the putamen, which is associated with a decline in the execution of complex motor tests. These tests could be early indicators of the ongoing dopaminergic deficit in this group at risk of PD.
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Ilundain Fundazioa, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergareche
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.|Ikerbasque. Basque Foundation for Science, Bilbao, Spain.
authors.forename: Maria Cruz
authors.initials: MC
authors.lastname: Rodríguez-Oroz
authors.affiliation: Ilundain Fundazioa, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Estanga
authors.affiliation: Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gorostidi
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Ilundain Fundazioa, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.|Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Castillo-Triviño
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martínez
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Mondragón
authors.affiliation: Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.|Neurology Service, Multidisciplinary Sleep Unit, Hospital Clínic and Institut d'Investigació Biomèdiques August Pi i Sunyer, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Gaig
authors.affiliation: Nuclear Medicine Service, Hospital Clinic de Barcelona, Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Hospital Clinic de Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lomeña
authors.affiliation: Unidad de Apoyo Metodológico. Hospital Universitario Donostia. Biodonostia Research Institute, REDISSEC, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sarasqueta
authors.affiliation: Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.|Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.affiliation: Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.|Ilundain Fundazioa, San Sebastian, Spain.|Neuroscience Area. Biodonostia Research Institute, Spain.|Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.|Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
authors.forename: José Félix
authors.initials: JF
authors.lastname: Martí-Massó
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D011699:Putamen / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D004298:Dopamine
keywords: DATSCAN; LRRK2; Parkinson's disease; R1441G; biomarkers