Symptom‐led staging for semantic and non‐fluent/agrammatic variants of primary progressive aphasia
Chris JD Hardy, Cathleen Taylor‐Rubin, Beatrice Taylor, Emma Harding, Aida Suárez González, Jessica Jiang, Laura Thompson, Rachel Kingma, Anthipa Chokesuwattanaskul, Ffion Walker, Suzie Barker, Emilie Brotherhood, Claire Waddington, Olivia Wood, Nikki Zimmermann, Nuriye Kupeli, Keir Yong, Paul M. Camic, Joshua Stott, Charles R. Marshall, Neil P. Oxtoby, Jonathan D. Rohrer, Anna Volkmer, Sebastian J. Crutch, Jason D. Warren
Abstract
INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer's disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid ("PPA-Squared"). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA. HIGHLIGHTS: We introduce new symptom-led perspectives on primary progressive aphasia (PPA). The focus is on non-fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non-verbal features of PPA and clinical trajectories is featured. We introduce a symptom-led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid.