Cognition endpoints for Parkinson's disease: A roadmap for developing patient-focused assessment tools to accelerate drug development.

Abstract

Cognitive dysfunction is a prevalent and impactful feature of Parkinson's disease (PD), with substantial heterogeneity in onset, severity, and progression, and a high lifetime risk of dementia. Despite its clinical importance, effective treatments and fit-for-purpose outcome measures remain limited. This article reports outcomes from a multi-stakeholder roundtable convened by The Michael J. Fox Foundation for Parkinson's Research, outlining priorities to advance patient-focused endpoints and improve clinical trial design to accelerate therapeutic development for cognitive dysfunction. In the context of the current understanding of cognitive impairment across the PD/dementia with Lewy bodies (DLB) spectrum and existing neuropsychological assessment approaches, recommendations are made regarding necessary literature reviews, including qualitative data and related conceptual models, disease models including pathophysiology and neuropsychological profile, and clinical outcome assessment (COA) reviews, including content validity, psychometrics, and fitness-for-purpose. Additionally, novel conceptual models of cognitive impairment across the normal, mild cognitive impairment (MCI) and dementia spectrum are needed and may require further qualitative evidence.