Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-26T19:22:56.523Z Has data issue: false hasContentIssue false
  • English
  • Français

Language Deficits as a Preclinical Window into Parkinson’s Disease: Evidence from Asymptomatic Parkin and Dardarin Mutation Carriers

Published online by Cambridge University Press:  16 February 2017

Adolfo M. García ,
Lucas Sedeño ,
Natalia Trujillo ,
Yamile Bocanegra ,
Diana Gomez ,
David Pineda ,
Andrés Villegas ,
Edinson Muñoz ,
William Arias  and
Agustín Ibáñez
Adolfo M. García
Affiliation:
Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive and Translational Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina Faculty of Elementary and Special Education (FEEyE), National University of Cuyo (UNCuyo), Mendoza, Argentina
Lucas Sedeño
Affiliation:
Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive and Translational Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
Natalia Trujillo
Affiliation:
Mental Health Group, School of Public Health, University of Antioquia (UDEA), Medellín, Colombia Group of Neuropsychology and Conduct (GRUNECO), Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia Neuroscience Group, Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia
Yamile Bocanegra
Affiliation:
Group of Neuropsychology and Conduct (GRUNECO), Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia Neuroscience Group, Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia
Diana Gomez
Affiliation:
Mental Health Group, School of Public Health, University of Antioquia (UDEA), Medellín, Colombia Neuroscience Group, Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia
David Pineda
Affiliation:
Group of Neuropsychology and Conduct (GRUNECO), Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia Neuroscience Group, Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia
Andrés Villegas
Affiliation:
Neuroscience Group, Faculty of Medicine, University of Antioquia (UDEA), Medellín, Colombia
Edinson Muñoz
Affiliation:
Departamento de Lingüística y Literatura, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, Chile
William Arias
Affiliation:
Molecular Genetics Laboratory, University of Antioquia (UDEA), Medellín, Colombia
Agustín Ibáñez*
Affiliation:
Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive and Translational Neuroscience (INCyT), INECO Foundation, Favaloro University, Buenos Aires, Argentina National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina Universidad Autónoma del Caribe, Barranquilla, Colombia Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibáñez, Santiago de Chile, Chile Centre of Excellence in Cognition and its Disorders, Australian Research Council (ACR), Macquarie University, Sydney, Australia
*
Correspondence and reprint requests to: Agustín Ibáñez, Institute of Cognitive and Translational Neuroscience & CONICET; Pacheco de Melo 1860, C1126AAB, Buenos Aires, Argentina. E-mail: aibanez@ineco.org.ar
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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)

Keywords

Sporadic Parkinson’s diseaseGenetic Parkinson’s diseasePARK2LRRK2Preclinical mutation carrierslanguage
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 23 , Special Issue 2: Special Issue: Motor Cognition , February 2017 , pp. 150 - 158
Copyright
Copyright © The International Neuropsychological Society 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Acosta-Baena, N., Sepulveda-Falla, D., Lopera-Gomez, C.M., Jaramillo-Elorza, M.C., Moreno, S., Aguirre-Acevedo, D.C., & Lopera, F. (2011). Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: A retrospective cohort study. The Lancet. Neurology, 10(3), 213–220. doi:10.1016/s1474-4422(10)70323-9 CrossRefGoogle ScholarPubMed
Angwin, A.J., Chenery, H.J., Copland, D.A., Murdoch, B.E., & Silburn, P.A. (2006). Self-paced reading and sentence comprehension in Parkinson’s disease. Journal of Neurolinguistics, 19(3), 239–252. doi:http://dx.doi.org/10.1016/j.jneuroling.2005.11.004 Google Scholar
Arcos-Burgos, M., & Muenke, M. (2002). Genetics of population isolates. Clinical Genetics, 61(4), 233–247. doi:10.1034/j.1399-0004.2002.610401.x Google Scholar
Azambuja, M.J., Radanovic, M., Haddad, M.S., Adda, C.C., Barbosa, E.R., & Mansur, L.L. (2012). Language impairment in Huntington’s disease. Arquivos de Neuro-psiquiatria, 70(6), 410–415. doi:S0004-282X2012000600006 [pii] CrossRefGoogle ScholarPubMed
Baez, S., Couto, B., Herrera, E., Bocanegra, Y., Trujillo-Orrego, N., Madrigal-Zapata, L., & Villegas, A. (2013). Tracking the cognitive, social, and neuroanatomical profile in early neurodegeneration: Type III Cockayne syndrome. Frontiers in Aging Neuroscience, 5, 80. doi:10.3389/fnagi.2013.00080 CrossRefGoogle ScholarPubMed
Bak, T.H. (2013). The neuroscience of action semantics in neurodegenerative brain diseases. Current Opinion in Neurology, 26(6), 671–677. doi:10.1097/wco.0000000000000039 Google Scholar
Bak, T.H., & Hodges, J.R. (2004). The effects of motor neurone disease on language: further evidence. Brain and Language, 89(2), 354–361. doi:10.1016/S0093-934X(03)00357-2 Google Scholar
Bak, T.H., Yancopoulou, D., Nestor, P.J., Xuereb, J.H., Spillantini, M.G., Pulvermuller, F., & Hodges, J.R. (2006). Clinical, imaging and pathological correlates of a hereditary deficit in verb and action processing. Brain, 129(Pt 2), 321–332. doi:10.1093/brain/awh701 CrossRefGoogle ScholarPubMed
Barsalou, L.W. (1999). Perceptual symbol systems. The Behavioral and Brain Sciences, 22(4), 577–609. discussion 610-560.Google Scholar
Bocanegra, Y., García, A.M., Pineda, D., Buriticá, O., Villegas, A., Lopera, F., & Ibáñez, A.M. (2015). Syntax, action verbs, action semantics, and object semantics in Parkinson’s disease: Dissociability, progression, and executive influences. Cortex, 69, 237–254.CrossRefGoogle ScholarPubMed
Braak, H., Del Tredici, K., Bratzke, H., Hamm-Clement, J., Sandmann-Keil, D., & Rub, U. (2002). Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). Journal of Neurology, 249(Suppl. 3), Iii/1–Iii/5.CrossRefGoogle ScholarPubMed
Button, K.S., Ioannidis, J.P.A., Mokrysz, C., Nosek, B.A., Flint, J., Robinson, E.S.J., & Munafo, M.R. (2013). Power failure: Why small sample size undermines the reliability of neuroscience. Nature Reviews. Neuroscience, 14(5), 365–376. doi:10.1038/nrn3475 Google Scholar
Cardona, J., Kargieman, L., Sinay, V., Gershanik, O., Gelormini, C., Amoruso, L., & Ibanez, A. (2014). How embodied is action language? Neurological evidence from motor diseases. Cognition, http://dx.doi.org/10.1016/j.cognition.2014.1002.1001 CrossRefGoogle ScholarPubMed
Cardona, J.F., Gershanik, O., Gelormini-Lezama, C., Houck, A.L., Cardona, S., Kargieman, L., & Ibanez, A. (2013). Action-verb processing in Parkinson’s disease: New pathways for motor-language coupling. Brain Structure & Function, 218, 1355–1373. doi:10.1007/s00429-013-0510-1 [doi] CrossRefGoogle ScholarPubMed
Cotelli, M., Borroni, B., Manenti, R., Zanetti, M., Arevalo, A., Cappa, S.F., & Padovani, A. (2007). Action and object naming in Parkinson’s disease without dementia. European Journal of Neurology, 14(6), 632–637. doi:ENE1797 [pii];10.1111/j.1468-1331.2007.01797.x [doi] Google Scholar
Espay, A.J., Spina, S., Houghton, D.J., Murrell, J.R., de Courten-Myers, G.M., Ghetti, B., & Litvan, I. (2011). Rapidly progressive atypical parkinsonism associated with frontotemporal lobar degeneration and motor neuron disease. Journal of Neurology, Neurosurgery, and Psychiatry, 82(7), 751–753. doi:10.1136/jnnp.2009.201608 Google Scholar
Friederici, A.D., Kotz, S.A., Werheid, K., Hein, G., & von Cramon, D.Y. (2003). Syntactic comprehension in Parkinson’s disease: Investigating early automatic and late integrational processes using event-related brain potentials. Neuropsychology, 17(1), 133–142.Google Scholar
Fujioka, S., Boeve, B.F., Parisi, J.E., Tacik, P., Aoki, N., Strongosky, A.J., & Wszolek, Z.K. (2014). A familial form of parkinsonism, dementia, and motor neuron disease: A longitudinal study. Parkinsonism & Related Disorders, 20(11), 1129–1134. doi:10.1016/j.parkreldis.2014.07.014 Google Scholar
Gallese, V., & Lakoff, G. (2005). The brain’s concepts: The role of the sensory-motor system in conceptual knowledge. Cognitive Neuropsychology, 22(3), 455–479. doi:714592738 [pii];10.1080/02643290442000310 Google Scholar
García, A. M., Carrillo, F., Orozco-Arroyave, J. R., Trujillo, N., Vargas Bonilla, J. F., Fittipaldi, S., Adolfi, F., Nöth, E., Sigman, M., Fernández Slezak, D., Ibáñez, A. & Cecchi, G. A. (2016). How language flows when movements don’t: An automated analysis of spontaneous discourse in Parkinson’s disease. Brain and Language, 162, 19–28.Google Scholar
García, A., & Ibáñez, A. (2014). Words in motion: Motor-language coupling in Parkinson’s disease. Translational Neuroscience, 5(2), 152–159. doi:10.2478/s13380-014-0218-6 Google Scholar
García, A.M., & Ibáñez, A. (2016). A touch with words: Dynamic synergies between manual actions and language. Neuroscience & Biobehavioral Reviews, 68, 59–95. doi:10.1016/j.neubiorev.2016.04.022 CrossRefGoogle ScholarPubMed
Goldwurm, S., Di Fonzo, A., Simons, E.J., Rohe, C.F., Zini, M., Canesi, M., & Bonifati, V. (2005). The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson’s disease and originates from a common ancestor. Journal of Medical Genetics, 42(11), e65. doi:10.1136/jmg.2005.035568 Google Scholar
Grossman, M., Cooke, A., DeVita, C., Lee, C., Alsop, D., Detre, J., & Hurtig, H.I. (2003). Grammatical and resource components of sentence processing in Parkinson’s disease: An fMRI study. Neurology, 60(5), 775–781.Google Scholar
Herrera, E., & Cuetos, F. (2012). Action naming in Parkinson’s disease patients on/off dopamine. Neuroscience Letters, 513(2), 219–222. doi:http://dx.doi.org/10.1016/j.neulet.2012.02.045 Google Scholar
Hochstadt, J., Nakano, H., Lieberman, P., & Friedman, J. (2006). The roles of sequencing and verbal working memory in sentence comprehension deficits in Parkinson’s disease. Brain and Language, 97(3), 243–257. doi:10.1016/j.bandl.2005.10.011 Google Scholar
Hughes, A.J., Daniel, S.E., Kilford, L., & Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry, 55(3), 181–184.Google Scholar
Ibanez, A., Cardona, J.F., Dos Santos, Y.V., Blenkmann, A., Aravena, P., Roca, M., & Bekinschtein, T. (2013). Motor-language coupling: Direct evidence from early Parkinson’s disease and intracranial cortical recordings. Cortex, 49(4), 968–984. doi:10.1016/j.cortex.2012.02.014 Google Scholar
Kargieman, L., Herrera, E., Baez, S., Garcia, A.M., Dottori, M., Gelormini, C., & Ibanez, A. (2014). Motor-language coupling in Huntington’s disease families. Frontiers of Aging and Neuroscience, 6, 122. doi:10.3389/fnagi.2014.00122 Google Scholar
Lee, C., Grossman, M., Morris, J., Stern, M.B., & Hurtig, H.I. (2003). Attentional resource and processing speed limitations during sentence processing in Parkinson’s disease. Brain and Language, 85(3), 347–356.Google Scholar
Lieberman, P., Kako, E., Friedman, J., Tajchman, G., Feldman, L.S., & Jiminez, E.B. (1992). Speech production, syntax comprehension, and cognitive deficits in Parkinson’s disease. Brain and Language, 43(2), 169–189.CrossRefGoogle ScholarPubMed
McKinlay, A., Grace, R.C., Dalrymple-Alford, J.C., & Roger, D. (2010). Characteristics of executive function impairment in Parkinson’s disease patients without dementia. Journal of the International Neuropsychological Society, 16(2), 268–277. doi:10.1017/s1355617709991299 CrossRefGoogle ScholarPubMed
Melloni, M., Sedeño, L., Hesse, E., García-Cordero, I., Mikulan, E., Plastino, A., & Ibáñez, A. (2015). Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson’s disease. Scientific Reports, 5, 11899.Google Scholar
Mercadillo, R.E., Galvez, V., Diaz, R., Hernandez-Castillo, C.R., Campos-Romo, A., Boll, M.C., & Fernandez-Ruiz, J. (2014). Parahippocampal gray matter alterations in spinocerebellar ataxia type 2 identified by voxel based morphometry. Journal of the Neurological Sciences, 347(1-2), 50–58. doi:10.1016/j.jns.2014.09.018 CrossRefGoogle ScholarPubMed
Nalls, M.A., Pankratz, N., Lill, C.M., Do, C.B., Hernandez, D.G., Saad, M., & Singleton, A.B. (2014). Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics, 46(9), 989–993. doi:10.1038/ng.3043 Google Scholar
Pineda-Trujillo, N., Apergi, M., Moreno, S., Arias, W., Lesage, S., Franco, A., & Ruiz-Linares, A. (2006). A genetic cluster of early onset Parkinson’s disease in a Colombian population. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 141b(8), 885–889. doi:10.1002/ajmg.b.30375 CrossRefGoogle Scholar
Pineda-Trujillo, N., Carvajal-Carmona, L.G., Buritica, O., Moreno, S., Uribe, C., Pineda, D., & Ruiz-Linares, A. (2001). A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile Parkinsonism in a population from North West Colombia. Neuroscience Letters, 298(2), 87–90.Google Scholar
Pulvermuller, F. (2005). Brain mechanisms linking language and action. Nature Reviews. Neuroscience, 6(7), 576–582. doi:nrn1706 [pii];10.1038/nrn1706 Google Scholar
Renda, M.M., Voigt, R.G., Babovic-Vuksanovic, D., Highsmith, W.E., Vinson, S.S., Sadowski, C.M., & Hagerman, R.J. (2014). Neurodevelopmental disabilities in children with intermediate and premutation range fragile X cytosine-guanine-guanine expansions. Journal of Child Neurology, 29(3), 326–330. doi:10.1177/0883073812469723 Google Scholar
Samii, A., Nutt, J.G., & Ransom, B.R. (2004). Parkinson’s disease. The Lancet, 363(9423), 1783–1793. doi:10.1016/S0140-6736(04)16305-8 Google Scholar
Svenningsson, P., Westman, E., Ballard, C., & Aarsland, D. (2012). Cognitive impairment in patients with Parkinson’s disease: Diagnosis, biomarkers, and treatment. The Lancet Neurology, 11(8), 697–707. doi:10.1016/S1474-4422(12)70152-7 Google Scholar
Torralva, T., Roca, M., Gleichgerrcht, E., Lopez, P., & Manes, F. (2009). INECO Frontal Screening (IFS): A brief, sensitive, and specific tool to assess executive functions in dementia. Journal of the International Neuropsychological Society, 15(5), 777–786. doi:10.1017/s1355617709990415 Google Scholar
Ullman, M. (2008). The role of memory systems in disorders of language. In B. Stemmer & H.A. Whitaker (Eds.), Handbook of the neuroscience of language (pp. 189–198). London: Elsevier.Google Scholar
Ullman, M.T. (2004). Contributions of memory circuits to language: The declarative/procedural model. Cognition, 92(1–2), 231–270. doi:10.1016/j.cognition.2003.10.008 CrossRefGoogle ScholarPubMed
Zanini, S., Tavano, A., Vorano, L., Schiavo, F., Gigli, G.L., Aglioti, S.M., &Fabbro, F. (2004). Greater syntactic impairments in native language in bilingual Parkinsonian patients. Journal of Neurology, Neurosurgery, and Psychiatry, 75(12), 1678–1681. doi:10.1136/jnnp.2003.018507 Google Scholar