DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2R1441G Parkinson's disease

• Published in: Movement disorders Vol. 31; no. 3; pp. 335 - 343
• Main Authors: Bergareche, Alberto, Rodriguez-Oroz, Maria Cruz, Estanga, Ainara, Gorostidi, Ana, Lopez de Munain, Adolfo, Castillo-Trivino, Tamara, Ruiz-Martinez, Javier, Mondragon, Elisabet, Gaig, Carles, Lomena, Francisco, Sarasqueta, Cristina, Tolosa, Eduardo, Marti-Masso, José Félix
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.03.2016
• Subjects: Movement disorders
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26478

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 123I-2[beta]-carbomethoxy-3[beta]-(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 123I-2[beta]-carbomethoxy-3[beta]-(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 123I-2[beta]-carbomethoxy-3[beta]-(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. © 2015 International Parkinson and Movement Disorder Society