TY - JOUR
T1 - Brain Atrophy Does Not Predict Clinical Progression in Progressive Supranuclear Palsy
AU - the PASSPORT Study Group, the AL-108-231 Investigators, the Arise Investigators, the Tauros MRI Investigators, the DESCRIBE-PSP group
AU - Quattrone, Andrea
AU - Franzmeier, Nicolai
AU - Huppertz, Hans Jürgen
AU - Seneca, Nicholas
AU - Petzold, Gabor C.
AU - Spottke, Annika
AU - Levin, Johannes
AU - Prudlo, Johannes
AU - Düzel, Emrah
AU - Aiba, Ikuko
AU - Antonini, Angelo
AU - Apetauerova, Diana
AU - Azulay, Jean Philippe
AU - Martinez, Ernest Balaguer
AU - Bang, Jee
AU - Barone, Paolo
AU - Barrett, Matthew
AU - Bega, Danny
AU - Berg, Daniela
AU - Corrales, Koldo Berganzo
AU - Bordelon, Yvette
AU - Boxer, Adam L.
AU - Brandt, Moritz
AU - Brueggemann, Norbert
AU - Castelnovo, Giovanni
AU - Ceravolo, Roberto
AU - Chuang, Rosalind
AU - Chung, Sun Ju
AU - Church, Alistair
AU - Corvol, Jean Christophe
AU - Cudia, Paola
AU - Dale, Marian
AU - Defebvre, Luc
AU - Drapier, Sophie
AU - Driver-Dunckley, Erika D.
AU - Ebersbach, Georg
AU - Eggert, Karla M.
AU - Ellenbogen, Aaron
AU - Eusebio, Alexandre
AU - Evans, Andrew H.
AU - Fedorova, Natalia
AU - Finger, Elizabeth
AU - Foubert-Samier, Alexandra
AU - Ghosh, Boyd
AU - Golbe, Lawrence
AU - Perez, Francisco Grandas
AU - Grossman, Murray
AU - Hall, Deborah
AU - Hamada, Kyoko
AU - Tuite, Paul
N1 - Publisher Copyright:
© 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2025/11
Y1 - 2025/11
N2 - 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.
AB - 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.
KW - atlas-based volumetry
KW - clinical trials
KW - outcome
KW - progression
KW - progressive supranuclear palsy
UR - https://www.scopus.com/pages/publications/105015523779
UR - https://www.scopus.com/pages/publications/105015523779#tab=citedBy
U2 - 10.1002/mds.70026
DO - 10.1002/mds.70026
M3 - Article
C2 - 40884249
AN - SCOPUS:105015523779
SN - 0885-3185
VL - 40
SP - 2517
EP - 2530
JO - Movement Disorders
JF - Movement Disorders
IS - 11
ER -