Spontaneous speech and language measures as predictive biomarkers of clinically meaningful disease progression and neurodegeneration in Huntington's disease
Puig-Davi, Arnau (Institut de Recerca Sant Pau)
Franch-Marti, Carla (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Pérez-Pérez, Jesús (Institut de Recerca Sant Pau)
Olmedo-Saura, Gonzalo (Institut de Recerca Sant Pau)
Rodríguez Antigüedad, Jon (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Vázquez-Oliver, Anna (Institut de Recerca Sant Pau)
Rivas Asensio, Elisa (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Perez-Carasol, Laura (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ruiz Barrio, Iñigo (Institut de Recerca Sant Pau)
Bojtos, Lidia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Sampedro, Frederic (Institut de Recerca Sant Pau)
Pagonabarraga Mora, Javier (Institut de Recerca Sant Pau)
Kulisevsky, Jaime (Institut de Recerca Sant Pau)
Martínez-Horta, Saul (Institut de Recerca Sant Pau)
Caler-Gameiro, Lara (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Rubio-Romera, Margarita (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ji, Yi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2026
Resum:	Huntington's disease (HD) is characterized by heterogeneous rates of clinical progression, complicating patient monitoring and clinical trial design. Although speech and language alterations are increasingly recognized as part of the HD cognitive phenotype, their value as short-term prognostic biomarkers of clinically meaningful disease progression and neurodegeneration remains unestablished. In this prospective 12-month longitudinal study, we investigated whether objectively quantified spontaneous speech and language measures predict short-term clinically meaningful progression and relate to biomarkers of neurodegeneration in HD. Eighty-six participants (42 manifest HD, 24 premanifest gene carriers, and 20 healthy controls) underwent baseline spontaneous speech assessment, structural MRI, and plasma neurofilament light chain (NfL) quantification. Clinically meaningful worsening was defined using validated minimal clinically important difference thresholds in the composite Unified Huntington's Disease Rating Scale (cUHDRS). Spontaneous speech and language measures progressively deteriorated across disease stages and were associated with reduced cortico-subcortical gray matter volume in distributed associative and integrative regions. In manifest HD, logistic regression analyses revealed that baseline language integrity independently predicted clinically meaningful worsening at 12 months (OR = 3. 840, 95% CI = 1. 46-13. 33; AUC = 0. 783). Combining speech-derived measures with plasma NfL improved discrimination accuracy of individuals with accelerated clinical progression (AUC = 0. 807). Spontaneous speech represents an early, accessible and sensitive marker of neurodegeneration in HD. The combination of speech and language derived measures and plasma NfL enables accurate identification of individuals at risk of accelerated, clinically meaningful disease progression, supporting their potential utility as short-term prognostic biomarkers for clinical trials enrichment and stratification.
Ajuts:	Instituto de Salud Carlos III PI21/01758
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biomarker ; Cognitive impairment ; Huntington's disease ; Neurodegeneration ; Speech
Publicat a:	Journal of Neural Transmission, 2026 , ISSN 1435-1463

DOI: 10.1007/s00702-026-03143-x
PMID: 41915164

11 p, 1.3 MB

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