Abstract Progressive supranuclear palsy is a rare neurodegenerative disease with no current disease-modifying treatments approved. Longitudinal research and clinical trials for progressive supranuclear palsy are ongoing and require reliable measures which are sensitive to disease progression. Despite susceptibility to subjective limitations clinical and cognitive assessments are the most used instruments in therapeutic trials in progressive supranuclear palsy. The objective of this review is to identify measures which have been studied longitudinally as measures of progression and which are suitable for use as clinical trial endpoints. We reviewed the measures currently used as trial endpoints, identifying the clinical, cognitive, fluid and imaging measures which have previously been studied longitudinally, and discussing current diagnostic and emerging measures which are yet to be studied longitudinally but which may be sensitive to disease progression. We found that many fluid and imaging measures require further research to validate their use as longitudinal measures of change, including emerging measures which have not yet been studied specifically in progressive supranuclear palsy. We also summarise the sample size estimates required to detect changes in a 2-arm, 52-week therapeutic trial and found that specific MRI volumes require the smallest sample sizes to detect change.
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