Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy

Costanza Pavone, Stephen W. Weigand, Farwa Ali, Heather M. Clark, Hugo Botha, Mary M. Machulda, Rodolfo Savica, Nha Trang Thu Pham, Rosalie M. Grijalva, Christopher G. Schwarz, Matthew L. Senjem, Federica Agosta, Massimo Filippi, Clifford R. Jack, Val J. Lowe, Keith A. Josephs, Jennifer L. Whitwell

Research output: Contribution to journalArticlepeer-review


Introduction: Progressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, although little is known about how these features progress over time. We aimed to assess the evolution of these core clinical features across variants and assess baseline clinical and neuroimaging predictors of progression. Methods: Ninety-three PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two visits 1-year apart, with baseline MRI and [18F]flortaucipir PET. We compared baseline and annualized rates of clinical change on the PSP Rating Scale (total, ocular motor, gait/midline scores) and Montreal Cognitive Assessment, across PSP-Richardson's, PSP-Cortical and PSP-Subcortical variants and assessed relationships between rates of change and baseline regional imaging. Results: Ocular motor scores differed across groups at baseline and follow-up, with lowest scores observed in PSP-subcortical, but no differences were observed in rate of change across groups. PSP Rating Scale total and gait/midline scores differed across groups at follow-up and in rates of change, with PSP-subcortical showing the least impairment and slowest progression. Greatest cognitive impairment was observed in PSP-Cortical. Sample size estimates for treatment trials differed across PSP variants. Greater baseline flortaucipir uptake, but not volume, of midbrain and motor cortex correlated with faster rates of clinical decline. Conclusion: The PSP Rating Scale and its subscores might be useful markers for the prognostic stratification of PSP variants. Flortaucipir imaging at baseline may help predict rate of decline.

Original languageEnglish (US)
Article number105290
JournalParkinsonism and Related Disorders
StatePublished - Feb 2023


  • Akinesia
  • Clinical progression
  • MRI
  • Ocular motor
  • Postural instability
  • Progressive supranuclear palsy
  • flortaucipir

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology


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