Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia

INTRODUCTIONHere 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. METHODSAn 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. RESULTSBoth 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). DISCUSSIONThis 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. HighlightsWe 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.

Automated summary

We aimed to create a symptom-led staging system for primary progressive aphasia (PPA) to address the challenges not captured by existing functional scales. An international PPA caregiver cohort was surveyed, and the feedback was analyzed to develop a prototype functional impairment scale called PPA-Squared. This study has implications for diagnostic guidelines, care pathways, trial design, and personalized prognosis and treatment for PPA.