Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease

ABSTRACT Objective Huntington's disease (HD) speech/language disorders have typically been attributed to motor and executive impairment due to striatal dysfunction. In‐depth study of linguistic skills and the role of extrastriatal structures in HD is scarce. This study aimed to explore the prof...

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Main Authors: Arnau Puig‐Davi, Carla Franch‐Marti, Iñigo Ruiz‐Barrio, Frederic Sampedro, Jesus Perez‐Perez, Jordi A. Matias‐Guiu, Fernando Cuetos, Gonzalo Olmedo‐Saura, Laura Perez‐Carasol, Andrea Horta‐Barba, Ignacio Aracil‐Bolaños, Javier Pagonabarraga, Jaime Kulisevsky, Saul Martinez‐Horta
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Annals of Clinical and Translational Neurology
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Online Access:https://doi.org/10.1002/acn3.70022
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author Arnau Puig‐Davi
Carla Franch‐Marti
Iñigo Ruiz‐Barrio
Frederic Sampedro
Jesus Perez‐Perez
Jordi A. Matias‐Guiu
Fernando Cuetos
Gonzalo Olmedo‐Saura
Laura Perez‐Carasol
Andrea Horta‐Barba
Ignacio Aracil‐Bolaños
Javier Pagonabarraga
Jaime Kulisevsky
Saul Martinez‐Horta
author_facet Arnau Puig‐Davi
Carla Franch‐Marti
Iñigo Ruiz‐Barrio
Frederic Sampedro
Jesus Perez‐Perez
Jordi A. Matias‐Guiu
Fernando Cuetos
Gonzalo Olmedo‐Saura
Laura Perez‐Carasol
Andrea Horta‐Barba
Ignacio Aracil‐Bolaños
Javier Pagonabarraga
Jaime Kulisevsky
Saul Martinez‐Horta
author_sort Arnau Puig‐Davi
collection DOAJ
description ABSTRACT Objective Huntington's disease (HD) speech/language disorders have typically been attributed to motor and executive impairment due to striatal dysfunction. In‐depth study of linguistic skills and the role of extrastriatal structures in HD is scarce. This study aimed to explore the profile of language compromise in HD and identify the structural neuroimaging correlates. Methods Language and structural correlates were assessed using the Mini Linguistic State Examination (MLSE) in 81 participants (20 HD‐ISS 0‐1, 40 HD‐ISS 2‐3 and 21 controls). Clinical and global cognition measures were also obtained. Imaging data included computed gray matter volume (GMV) and cortical thickness (CTh) values extracted from a general linear model with the MLSE. Correlation analyses were performed with the language components of the MLSE. Multivariate regression analyses were used to explore the predictive ability of the language components on GMV and CTh loss. Results HD individuals showed impaired MLSE performance (84.5 ± 12.8), particularly in syntax, motor speech, and to a lesser extent, semantics and phonology. Significant associations were found between linguistic performance and the structural integrity of nodes within the temporo‐parietal, fronto‐parietal, and fronto‐striatal lexical‐semantic and syntactic networks. Correlation analyses linked motor speech and syntax with predominantly left fronto‐striatal GMV and CTh clusters, while semantics had a bilateral fronto‐parietal topography. Multivariate regression analyses showed language domains as independent contributing factors of GMV and CTh loss in classical language‐related regions. Interpretation Language impairment is an integral part of the HD cognitive phenotype, with severity associated with structural disintegration in extensive cortico‐subcortical territories involved in language production and processing.
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spelling doaj-art-0bc537a5b55d4272bcc8c4d945d7ac0f2025-08-20T03:45:40ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-06-011261201121310.1002/acn3.70022Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's DiseaseArnau Puig‐Davi0Carla Franch‐Marti1Iñigo Ruiz‐Barrio2Frederic Sampedro3Jesus Perez‐Perez4Jordi A. Matias‐Guiu5Fernando Cuetos6Gonzalo Olmedo‐Saura7Laura Perez‐Carasol8Andrea Horta‐Barba9Ignacio Aracil‐Bolaños10Javier Pagonabarraga11Jaime Kulisevsky12Saul Martinez‐Horta13Institute of Neuroscience Universitat Autònoma de Barcelona (UAB) Bellaterra SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainInstitute of Neuroscience Universitat Autònoma de Barcelona (UAB) Bellaterra SpainDepartment of Neurology Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdiSSC). Universidad Complutense Madrid SpainFaculty of Psychology University of Oviedo Oviedo SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainMovement Disorders Unit, Neurology Department Hospital de la Santa Creu i Sant Pau Barcelona SpainInstitute of Neuroscience Universitat Autònoma de Barcelona (UAB) Bellaterra SpainInstitute of Neuroscience Universitat Autònoma de Barcelona (UAB) Bellaterra SpainABSTRACT Objective Huntington's disease (HD) speech/language disorders have typically been attributed to motor and executive impairment due to striatal dysfunction. In‐depth study of linguistic skills and the role of extrastriatal structures in HD is scarce. This study aimed to explore the profile of language compromise in HD and identify the structural neuroimaging correlates. Methods Language and structural correlates were assessed using the Mini Linguistic State Examination (MLSE) in 81 participants (20 HD‐ISS 0‐1, 40 HD‐ISS 2‐3 and 21 controls). Clinical and global cognition measures were also obtained. Imaging data included computed gray matter volume (GMV) and cortical thickness (CTh) values extracted from a general linear model with the MLSE. Correlation analyses were performed with the language components of the MLSE. Multivariate regression analyses were used to explore the predictive ability of the language components on GMV and CTh loss. Results HD individuals showed impaired MLSE performance (84.5 ± 12.8), particularly in syntax, motor speech, and to a lesser extent, semantics and phonology. Significant associations were found between linguistic performance and the structural integrity of nodes within the temporo‐parietal, fronto‐parietal, and fronto‐striatal lexical‐semantic and syntactic networks. Correlation analyses linked motor speech and syntax with predominantly left fronto‐striatal GMV and CTh clusters, while semantics had a bilateral fronto‐parietal topography. Multivariate regression analyses showed language domains as independent contributing factors of GMV and CTh loss in classical language‐related regions. Interpretation Language impairment is an integral part of the HD cognitive phenotype, with severity associated with structural disintegration in extensive cortico‐subcortical territories involved in language production and processing.https://doi.org/10.1002/acn3.70022brain structurecognitive phenotypeHuntington's diseaselanguageneuroimaging
spellingShingle Arnau Puig‐Davi
Carla Franch‐Marti
Iñigo Ruiz‐Barrio
Frederic Sampedro
Jesus Perez‐Perez
Jordi A. Matias‐Guiu
Fernando Cuetos
Gonzalo Olmedo‐Saura
Laura Perez‐Carasol
Andrea Horta‐Barba
Ignacio Aracil‐Bolaños
Javier Pagonabarraga
Jaime Kulisevsky
Saul Martinez‐Horta
Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
Annals of Clinical and Translational Neurology
brain structure
cognitive phenotype
Huntington's disease
language
neuroimaging
title Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
title_full Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
title_fullStr Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
title_full_unstemmed Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
title_short Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
title_sort early language impairment as an integral part of the cognitive phenotype in huntington s disease
topic brain structure
cognitive phenotype
Huntington's disease
language
neuroimaging
url https://doi.org/10.1002/acn3.70022
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