Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy

Area of Science:

• Neuroscience
• Neurology

Background:

• Progressive supranuclear palsy (PSP) presents with diverse clinical variants, each characterized by distinct ocular motor, postural instability, akinesia, and cognitive dysfunctions.
• Understanding the longitudinal progression of these core clinical features across different PSP variants is crucial for effective patient management and therapeutic development.
• Limited data exists on how these key PSP symptoms evolve over time and which baseline factors predict disease trajectory.

Purpose of the Study:

• To investigate the temporal evolution of core clinical features in patients with different Progressive supranuclear palsy variants.
• To identify baseline clinical and neuroimaging predictors associated with the rate of disease progression in PSP.
• To compare the progression rates across PSP-Richardson's, PSP-Cortical, and PSP-Subcortical variants.

Main Methods:

• Ninety-three PSP patients were evaluated at baseline and after a 1-year follow-up, including clinical assessments using the PSP Rating Scale and Montreal Cognitive Assessment.
• Baseline magnetic resonance imaging (MRI) and [18F]flortaucipir positron emission tomography (PET) scans were acquired for all participants.
• Statistical analyses compared baseline scores and annualized rates of change across PSP variants and correlated imaging markers with clinical progression.

Main Results:

• Ocular motor scores varied significantly across PSP variants at baseline and follow-up, with PSP-subcortical exhibiting the least impairment.
• PSP-subcortical variant demonstrated the slowest progression in PSP Rating Scale total and gait/midline scores compared to other variants.
• Increased baseline [18F]flortaucipir uptake in the midbrain and motor cortex, but not regional volume, correlated with accelerated clinical decline.

Conclusions:

• The PSP Rating Scale and its subscores can serve as valuable prognostic markers for stratifying PSP variants.
• [18F]flortaucipir PET imaging at baseline shows potential for predicting the rate of clinical decline in Progressive supranuclear palsy.
• Findings aid in refining sample size calculations for future clinical trials targeting specific PSP variants.