Longitudinal cognitive outcomes in two progressive supranuclear palsy clinical trials

INTRODUCTION: Progressive supranuclear palsy (PSP) causes executive dysfunction, fluency deficits, and behavioral changes. We examined longitudinal changes in PSP cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). METHODS: Using the RBANS and executive function and fluency tests from 486 and 377 participants in the PASSPORT (NCT03068468) and tilavonemab (NCT02985879) clinical trials, we assessed linear mixed models of cognitive subtest score change, controlling for disease duration, age, sex, and treatment group. RESULTS: The greatest declines occurred in subtests assessing visuospatial (figure copy, figure recall), executive function (Color Trails, coding), and fluency (primarily semantic fluency), although controlling for motor and ocular motor disability reduced the magnitude of score decline. Subtests assessing immediate and delayed memory (story recall, story memory, list recall, list recognition) declined slowly or not at all. DISCUSSION: Cognition in PSP is characterized by declines in executive, visuospatial function, and fluency, with relative preservation of memory.