title: Language Deficits as a Preclinical Window into Parkinson's Disease: Evidence from Asymptomatic Parkin and Dardarin Mutation Carriers.
abstract: The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease.
  
  
  
  We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate.
  
  
  
  The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load.
  
  
  
  We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. (JINS, 2017, 23, 150-158).
authors.affiliation: 1Laboratory of Experimental Psychology and Neuroscience (LPEN),Institute of Cognitive and Translational Neuroscience (INCyT),INECO Foundation,Favaloro University,Buenos Aires,Argentina.
authors.forename: Adolfo M
authors.initials: AM
authors.lastname: García
authors.affiliation: 1Laboratory of Experimental Psychology and Neuroscience (LPEN),Institute of Cognitive and Translational Neuroscience (INCyT),INECO Foundation,Favaloro University,Buenos Aires,Argentina.
authors.forename: Lucas
authors.initials: L
authors.lastname: Sedeño
authors.affiliation: 4Mental Health Group,School of Public Health,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Trujillo
authors.affiliation: 5Group of Neuropsychology and Conduct (GRUNECO), Faculty of Medicine,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: Yamile
authors.initials: Y
authors.lastname: Bocanegra
authors.affiliation: 4Mental Health Group,School of Public Health,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: Diana
authors.initials: D
authors.lastname: Gomez
authors.affiliation: 5Group of Neuropsychology and Conduct (GRUNECO), Faculty of Medicine,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: David
authors.initials: D
authors.lastname: Pineda
authors.affiliation: 6Neuroscience Group, Faculty of Medicine,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: Andrés
authors.initials: A
authors.lastname: Villegas
authors.affiliation: 7Departamento de Lingüística y Literatura, Facultad de Humanidades,Universidad de Santiago de Chile,Santiago,Chile.
authors.forename: Edinson
authors.initials: E
authors.lastname: Muñoz
authors.affiliation: 8Molecular Genetics Laboratory,University of Antioquia (UDEA),Medellín,Colombia.
authors.forename: William
authors.initials: W
authors.lastname: Arias
authors.affiliation: 1Laboratory of Experimental Psychology and Neuroscience (LPEN),Institute of Cognitive and Translational Neuroscience (INCyT),INECO Foundation,Favaloro University,Buenos Aires,Argentina.
authors.forename: Agustín
authors.initials: A
authors.lastname: Ibáñez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D007806:Language Disorders / Q000209:etiology* / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D008037:Linguistics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D012660:Semantics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Genetic Parkinson’s disease; LRRK2; PARK2; Preclinical mutation carriers; Sporadic Parkinson’s disease; language