Early Language Impairment as an Integral Part of the Cognitive Phenotype in Huntington's Disease
Puig-Davi, Arnau (Universitat Autònoma de Barcelona. Institut de Neurociències)
Franch-Marti, Carla (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ruiz Barrio, Iñigo (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sampedro, Frederic (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Pérez-Pérez, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Matias-Guiu, Jordi A. (Hospital Clínico San Carlos (Madrid))
Cuetos Vega, Fernando (Universidad de Oviedo)
Olmedo-Saura, Gonzalo (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Perez-Carasol, Laura (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Horta, Andrea (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Aracil-Bolaños, Ignacio (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Pagonabarraga Mora, Javier (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Kulisevsky, Jaime (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Martínez-Horta, Saul (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))

Data:	2025
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI21/01758
Nota:	This study was funded by Fondo de Investigaciones Sanitarias from the Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional grant #PI21/01758. A.P.\u2010D. is the recipient of a predoctoral grant from the Government of Andorra (ATC027\u2010AND/2021), I.R.\u2010B. is the recipient of a Rio Hortega contract from ISCIII (CM22/00072), and I.A.\u2010B. is the recipient of a Juan Rod\u00E9s contract from ISCIII (JR22/00059). None of the funders played any role at any stage of the study. We thank patients and caregivers for their effort and commitment to the study.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Brain structure ; Cognitive phenotype ; Huntington's disease ; Language ; Neuroimaging
Publicat a:	Annals of clinical and translational neurology, Vol. 12 Núm. 6 (june 2025) , p. 1201-1213, ISSN 2328-9503

DOI: 10.1002/acn3.70022
PMID: 40244831

13 p, 1.2 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats