Journal Article

Language impairment is associated with faster progression in progressive supranuclear palsy‐Richardson syndrome

Garcia‐Cordero, Indira, Pantelyat, Alexander, McFarland, Nikolaus, Litvan, Irene, Swan, Matthew, Boxer, Adam, Tartaglia, Maria Carmela, Bayram, Ece, Dale, Marian L., Xie, Tao, Vargas‐Gonzalez, Juan Camilo, Rodriguez‐Porcel, Federico, Stephen, Christopher D., Kang, Kyurim, Hadian, Mohsen, Golbe, Lawrence I., Gunzler, Douglas, Wills, Anne‐Marie, Couto, Blas, Iyer, Jay, Lang, Anthony

2025

Overview

INTRODUCTION Cognitive impairment is common but often overlooked due to motor symptoms in progressive supranuclear palsy‐Richardson syndrome (PSP‐RS). This study investigates whether cognitive deficits predict disease progression in PSP‐RS. METHODS A total of 146 PSP‐RS from the Tilavonemab trial were evaluated at baseline and over 52 weeks using the PSP‐Rating Scale (PSPRS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Unified Parkinson's Disease Rating Scale Part‐II (UPDRS‐II). Multiple linear regression analyses were performed between the RBANS, UPDRS‐II, and the PSPRS change. Clinical scores, gray matter volumes, and neurofilament‐light chain (NfL) were compared using analyses of covariance (ANCOVAs) and linear mixed models between language score‐groups. RESULTS Lower RBANS‐language at baseline predicted greater PSPRS worsening over time. The low language‐score group showed poorer cognitive performance, elevated NfL, and reduced gray matter volume in language‐related areas. DISCUSSION Speech/language deficits predict worse prognosis in PSP‐RS, emphasizing the value of including language scores in clinical trials. Highlights Speech and language deficits predict a worse prognosis in progressive supranuclear palsy‐Richardson syndrome (PSP‐RS). Lower language scores are associated with worse cognitive performance over time. Lower language scores related to higher neurofilament‐light chain (NfL) at baseline. The low language‐score group presented greater atrophy in language‐related brain areas. Stratifying PSP‐RS cases using language scores may improve clinical trials.

• Publisher: John Wiley and Sons Inc
• Subject: Aged / Brain - diagnostic imaging / Brain - pathology / cognition / Disease Progression / Female / Gray Matter - diagnostic imaging / Gray Matter - pathology / gray matter volume / Humans / language / Language Disorders - diagnostic imaging / Language Disorders - etiology / Magnetic Resonance Imaging / Male / Middle Aged / Neurofilament Proteins - metabolism / neurofilament‐light chain / Neuropsychological Tests / PSP‐Rating Scale / PSP‐Richardson syndrome / RBANS / Supranuclear Palsy, Progressive - complications / Supranuclear Palsy, Progressive - diagnostic imaging / Supranuclear Palsy, Progressive - drug therapy / Supranuclear Palsy, Progressive - pathology