DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2 R1441G Parkinson's disease. Issue 3 (21st December 2015)

• Record Type: Journal Article
• Authors: Bergareche, Alberto; Rodríguez‐Oroz, Maria Cruz; Estanga, Ainara; Gorostidi, Ana; López de Munain, Adolfo; Castillo‐Triviño, Tamara; Ruiz‐Martínez, Javier; Mondragón, Elisabet; Gaig, Carles; Lomeña, Francisco; Sarasqueta, Cristina; Tolosa, Eduardo; Martí‐Massó, José Félix
• Is Part Of: Movement disorders. Volume 31:Issue 3(2016)
• Page Start: 335
• Page End: 343
• Publication Date: 2015-12-21
• Subjects: Parkinson's disease -- DATSCAN -- biomarkers -- LRRK2 -- R1441G; Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.26478
• Languages: English
• ISSNs: 0885-3185

Abstract

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. © 2015 International Parkinson and Movement Disorder Society