PMID- 26686514
OWN - NLM
STAT- MEDLINE
DCOM- 20161215
LR  - 20161230
IS  - 1531-8257 (Electronic)
IS  - 0885-3185 (Linking)
VI  - 31
IP  - 3
DP  - 2016 Mar
TI  - DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G
      Parkinson's disease.
PG  - 335-43
LID - 10.1002/mds.26478 [doi]
AB  - 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-2beta-carbomethoxy-3beta-(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-2beta-carbomethoxy-3beta-(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-2beta-carbomethoxy-3beta-(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.
CI  - (c) 2015 International Parkinson and Movement Disorder Society.
FAU - Bergareche, Alberto
AU  - Bergareche A
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Ilundain Fundazioa, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
FAU - Rodriguez-Oroz, Maria Cruz
AU  - Rodriguez-Oroz MC
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
AD  - Ikerbasque. Basque Foundation for Science, Bilbao, Spain.
FAU - Estanga, Ainara
AU  - Estanga A
AD  - Ilundain Fundazioa, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
FAU - Gorostidi, Ana
AU  - Gorostidi A
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
FAU - Lopez de Munain, Adolfo
AU  - Lopez de Munain A
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Ilundain Fundazioa, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
AD  - Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
FAU - Castillo-Trivino, Tamara
AU  - Castillo-Trivino T
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
FAU - Ruiz-Martinez, Javier
AU  - Ruiz-Martinez J
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
FAU - Mondragon, Elisabet
AU  - Mondragon E
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
FAU - Gaig, Carles
AU  - Gaig C
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
AD  - Neurology Service, Multidisciplinary Sleep Unit, Hospital Clinic and Institut
      d'Investigacio Biomediques August Pi i Sunyer, Spain.
FAU - Lomena, Francisco
AU  - Lomena F
AD  - Nuclear Medicine Service, Hospital Clinic de Barcelona, Centro de Investigacion
      Biomedica en Red Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN),
      Hospital Clinic de Barcelona, Spain.
FAU - Sarasqueta, Cristina
AU  - Sarasqueta C
AD  - Unidad de Apoyo Metodologico. Hospital Universitario Donostia. Biodonostia
      Research Institute, REDISSEC, Spain.
FAU - Tolosa, Eduardo
AU  - Tolosa E
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
AD  - Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, Spain.
FAU - Marti-Masso, Jose Felix
AU  - Marti-Masso JF
AD  - Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain.
AD  - Ilundain Fundazioa, San Sebastian, Spain.
AD  - Neuroscience Area. Biodonostia Research Institute, Spain.
AD  - Centro de Investigacion Biomedicas en Red Enfermedades Neurodegenerativas
      (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain.
AD  - Department of Neuroscience, University of the Basque Country UPV/EHU, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151221
PL  - United States
TA  - Mov Disord
JT  - Movement disorders : official journal of the Movement Disorder Society
JID - 8610688
RN  - 0 (Biomarkers)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - EC 2.7.11.1 (LRRK2 protein, human)
RN  - EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/metabolism
MH  - Dopamine/metabolism
MH  - Dopamine Plasma Membrane Transport Proteins/metabolism
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Neuropsychological Tests
MH  - Parkinson Disease/*diagnosis/*genetics
MH  - Putamen/*metabolism
MH  - Tomography, Emission-Computed, Single-Photon/methods
OTO - NOTNLM
OT  - DATSCAN
OT  - LRRK2
OT  - Parkinson's disease
OT  - R1441G
OT  - biomarkers
EDAT- 2015/12/22 06:00
MHDA- 2016/12/16 06:00
CRDT- 2015/12/22 06:00
PHST- 2015/04/15 00:00 [received]
PHST- 2015/10/08 00:00 [revised]
PHST- 2015/10/11 00:00 [accepted]
PHST- 2015/12/22 06:00 [entrez]
PHST- 2015/12/22 06:00 [pubmed]
PHST- 2016/12/16 06:00 [medline]
AID - 10.1002/mds.26478 [doi]
PST - ppublish
SO  - Mov Disord. 2016 Mar;31(3):335-43. doi: 10.1002/mds.26478. Epub 2015 Dec 21.