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. 2025 Aug 30.
doi: 10.1002/mds.70026. Online ahead of print.

Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy

Andrea Quattrone  1   2   3 , Nicolai Franzmeier  4   5   6 , Hans-Jürgen Huppertz  7 , Nicholas Seneca  8 , Gabor C Petzold  9   10 , Annika Spottke  9   11 , Johannes Levin  1   5   12 , Johannes Prudlo  13   14 , Emrah Düzel  15   16   17 ; PASSPORT Study Group, the AL‐108‐231 Investigators, the Arise Investigators, the Tauros MRI Investigators, the DESCRIBE‐PSP group; Günter U Höglinger  1   5   12
Collaborators, Affiliations

Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy

Andrea Quattrone et al. Mov Disord. .

Abstract

Background: Clinical progression rate is the typical primary endpoint measure in progressive supranuclear palsy (PSP) clinical trials.

Objectives: This longitudinal multicohort study investigated whether baseline clinical severity and regional brain atrophy could predict clinical progression in PSP-Richardson's syndrome (PSP-RS).

Methods: 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.

Results: 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 (R2 <0.15).

Conclusions: 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.

Keywords: atlas‐based volumetry; clinical trials; outcome; progression; progressive supranuclear palsy.

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References

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