Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy.
Authors
Affiliations (17)
Affiliations (17)
- Department of Neurology, University Hospital, LMU Munich, Munich, Germany.
- Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.
- Neuroscience Research Centre, Magna Graecia University, Catanzaro, Italy.
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU, Munich, Germany.
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
- Department of Psychiatry and Neurochemistry, University of Gothenburg, The Sahlgrenska Academy, Institute of Neuroscience and Physiology, Mölndal and Gothenburg, Sweden.
- Swiss Epilepsy Clinic, Klinik Lengg, Zurich, Switzerland.
- Precision Medicine-Neuroscience, AbbVie Inc, North Chicago, Illinois, USA.
- German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
- Division of Vascular Neurology, Department of Neurology, University Hospital Bonn, Bonn, Germany.
- Department of Neurology, University of Bonn, Bonn, Germany.
- German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany.
- German Center for Neurodegenerative Diseases (DZNE), Rostock-Greifswald, Germany.
- Department of Neurology, University Medical Centre, Rostock, Germany.
- German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
- Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
- Institute of Cognitive Neuroscience, University College London, London, United Kingdom.
Abstract
Clinical progression rate is the typical primary endpoint measure in progressive supranuclear palsy (PSP) clinical trials. This longitudinal multicohort study investigated whether baseline clinical severity and regional brain atrophy could predict clinical progression in PSP-Richardson's syndrome (PSP-RS). PSP-RS patients (n = 309) from the placebo arms of clinical trials (NCT03068468, NCT01110720, NCT02985879, NCT01049399) and DescribePSP cohort were included. We investigated associations of baseline clinical and volumetric magnetic resonance imaging (MRI) data with 1-year longitudinal PSP rating scale (PSPRS) change. Machine learning (ML) models were tested to predict individual clinical trajectories. PSP-RS patients showed a mean PSPRS score increase of 10.3 points/yr. The frontal lobe volume showed the strongest association with subsequent clinical progression (β: -0.34, P < 0.001). However, ML models did not accurately predict individual progression rates (R<sup>2</sup> <0.15). Baseline clinical severity and brain atrophy could not predict individual clinical progression, suggesting no need for MRI-based stratification of patients in future PSP trials. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.