Alberto Bergareche1,2,3,4, Maria Cruz Rodríguez-Oroz1,3,4,5, Ainara Estanga2,3,6, Ana Gorostidi3,4, Adolfo López de Munain1,2,3,4,6, Tamara Castillo-Triviño1,3, Javier Ruiz-Martínez1,3,4, Elisabet Mondragón1,3, Carles Gaig4,7, Francisco Lomeña8, Cristina Sarasqueta9, Eduardo Tolosa4,10, José Félix Martí-Massó1,2,3,4,6. 1. Neurology Service, Hospital Universitario Donostia, San Sebastian, Spain. 2. Ilundain Fundazioa, San Sebastian, Spain. 3. Neuroscience Area. Biodonostia Research Institute, Spain. 4. Centro de Investigación Biomédicas en Red Enfermedades Neurodegenerativas (CIBERNED), Institute Carlos III, Ministry of Economy and Competitiveness, Spain. 5. Ikerbasque. Basque Foundation for Science, Bilbao, Spain. 6. Department of Neuroscience, University of the Basque Country UPV/EHU, Spain. 7. Neurology Service, Multidisciplinary Sleep Unit, Hospital Clínic and Institut d'Investigació Biomèdiques August Pi i Sunyer, Spain. 8. Nuclear Medicine Service, Hospital Clinic de Barcelona, Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Hospital Clinic de Barcelona, Spain. 9. Unidad de Apoyo Metodológico. Hospital Universitario Donostia. Biodonostia Research Institute, REDISSEC, Spain. 10. Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, Spain.
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.
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: Tanya Simuni; Liz Uribe; Hyunkeun Ryan Cho; Chelsea Caspell-Garcia; Christopher S Coffey; Andrew Siderowf; John Q Trojanowski; Leslie M Shaw; John Seibyl; Andrew Singleton; Arthur W Toga; Doug Galasko; Tatiana Foroud; Duygu Tosun; Kathleen Poston; Daniel Weintraub; Brit Mollenhauer; Caroline M Tanner; Karl Kieburtz; Lana M Chahine; Alyssa Reimer; Samantha J Hutten; Susan Bressman; Kenneth Marek Journal: Lancet Neurol Date: 2019-10-31 Impact factor: 44.182
Authors: Morad Elshehabi; Katrin S Maier; Sandra E Hasmann; Susanne Nussbaum; Heinz Herbst; Tanja Heger; Daniela Berg; Markus A Hobert; Walter Maetzler Journal: Front Aging Neurosci Date: 2016-01-27 Impact factor: 5.750
Authors: Daryl J Wile; Pankaj A Agarwal; Michael Schulzer; Edwin Mak; Katherine Dinelle; Elham Shahinfard; Nasim Vafai; Kazuko Hasegawa; Jing Zhang; Jessamyn McKenzie; Nicole Neilson; Audrey Strongosky; Ryan J Uitti; Mark Guttman; Cyrus P Zabetian; Yu-Shin Ding; Mike Adam; Jan Aasly; Zbigniew K Wszolek; Matthew Farrer; Vesna Sossi; A Jon Stoessl Journal: Lancet Neurol Date: 2017-03-20 Impact factor: 44.182