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

Indira Garcia-Cordero¹, Juan Camilo Vargas-Gonzalez¹, Mohsen Hadian¹, Ece Bayram², Federico Rodriguez-Porcel³, Blas Couto⁴, Jay Iyer⁵, Lawrence I Golbe^{6

7}, Christopher D Stephen⁸, Alexander Pantelyat⁹, Marian L Dale^{10

11}, Nikolaus McFarland¹², Tao Xie¹³, Matthew Swan¹⁴, Kyurim Kang¹⁵, Douglas Gunzler¹⁶, Anne-Marie Wills⁸, Adam Boxer¹⁷, Irene Litvan¹⁸, Anthony Lang^{19

20}, Maria Carmela Tartaglia^{1

19

20}

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
² Movement Disorders Center, Department of Neurology, University of Colorado Anschutz, Aurora, Colorado, USA.
³ Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.
⁴ Institute of Cognitive and Translational Neuroscience (INCyT-INECO-CONICET), Favaloro University Hospital, Buenos Aires, Argentina.
⁵ Departments of Molecular and Cellular Biology and Statistics, Harvard University, Cambridge, Massachusetts, USA.
⁶ Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
⁷ CurePSP, Inc., New York, New York, USA.
⁸ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
¹¹ VA Medical Center PADRECC, Portland, Oregon, USA.
¹² Department of Neurology, Norman Fixel Institute for Neurological Diseases, College of Medicine, University of Florida, Gainesville, Florida, USA.
¹³ Department of Neurology, University of Chicago Medicine, Chicago, Illinois, USA.
¹⁴ Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.
¹⁵ Music and Health Science Research Collaboratory (MaHRC), Faculty of Music, University of Toronto, Toronto, ON, Canada.
¹⁶ Population Health and Equity Research Institute, Center for Health Care Research and Policy, MetroHealth Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
¹⁷ Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA.
¹⁸ Department of Neurosciences, University of California San Diego, San Diego, California, USA.
¹⁹ The Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto, ON, Canada.
²⁰ Rossy PSP Program, University Health Network and the University of Toronto, Toronto, ON, Canada.

PMID: 40684253
PMCID: PMC12276069
DOI: 10.1002/alz.70485

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

Indira Garcia-Cordero et al. Alzheimers Dement. 2025 Jul.

. 2025 Jul;21(7):e70485.

doi: 10.1002/alz.70485.

Authors

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
² Movement Disorders Center, Department of Neurology, University of Colorado Anschutz, Aurora, Colorado, USA.
³ Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.
⁴ Institute of Cognitive and Translational Neuroscience (INCyT-INECO-CONICET), Favaloro University Hospital, Buenos Aires, Argentina.
⁵ Departments of Molecular and Cellular Biology and Statistics, Harvard University, Cambridge, Massachusetts, USA.
⁶ Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
⁷ CurePSP, Inc., New York, New York, USA.
⁸ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
¹¹ VA Medical Center PADRECC, Portland, Oregon, USA.
¹² Department of Neurology, Norman Fixel Institute for Neurological Diseases, College of Medicine, University of Florida, Gainesville, Florida, USA.
¹³ Department of Neurology, University of Chicago Medicine, Chicago, Illinois, USA.
¹⁴ Department of Neurology, Mount Sinai Beth Israel, and Icahn School of Medicine, New York, New York, USA.
¹⁵ Music and Health Science Research Collaboratory (MaHRC), Faculty of Music, University of Toronto, Toronto, ON, Canada.
¹⁶ Population Health and Equity Research Institute, Center for Health Care Research and Policy, MetroHealth Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
¹⁷ Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA.
¹⁸ Department of Neurosciences, University of California San Diego, San Diego, California, USA.
¹⁹ The Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto, ON, Canada.
²⁰ Rossy PSP Program, University Health Network and the University of Toronto, Toronto, ON, Canada.

PMID: 40684253
PMCID: PMC12276069
DOI: 10.1002/alz.70485

Abstract

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.

Keywords: PSP‐Rating Scale; PSP‐Richardson syndrome; RBANS; cognition; disease progression; gray matter volume; language; neurofilament‐light chain.

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Conflict of interest statement

The other authors declare no competing interests. Author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
Differences between the low (blue) and high (red) language‐score groups. (A) Visual representation of the significant interaction between time and group on the PSPRS scores. Shaded areas denote standard errors of the model. (B) ROIs regions and means of the gray matter z‐score volumes for each ROI over time. The highlighted areas in yellow represent the different brain regions comprising each ROI. Only the left language ROI (B.1) presented a significant group effect. No group or interaction effects were observed in the right language (B.2), the attention (B.3), the memory (B.4), or the visuoconstructional (B.5) ROIs. Error bars represent standard deviations. GM, gray matter; PSPRS, Progressive Supranuclear Palsy Rating Scale; ROI, region of interest.

See this image and copyright information in PMC

References

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

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

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