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

Abstract

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.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.

Symptom‐based staging for logopenic variant primary progressive aphasia

“…Following previously described methods [8], two of the authors (including non-verbal thinking and personality, B1; and personal care and wellbeing, B2). Qualitative input on these symptoms was gathered from members of the UK national PPA Support Group [10], via an online survey hosted on the Opinio platform.…”

“…Language and communication functions are not comprehensively captured by standard clinical rating scales developed for typical AD [7]. It has recently been shown that symptom-based staging informed by lived experience is feasible for other primary progressive aphasia (PPA) syndromes [8]; however, a similar tool to signpost the evolution of communication problems is lacking for lvPPA. This is particularly urgent with the advent of disease-modifying therapies for AD, as the eligibility of individuals with lvPPA and other forms of 'atypical' AD remains unclear [9] and may be confounded by misleadingly poor performance on standard, language-weighted cognitive tests.…”

“…In the final section of the survey, respondents were presented with a representative list of symptoms present (1) in the other PPA variants on which there has been a previous publication [8] (sampling each of the domains A, B1 and B2) and (2) (mainly as an internal 'control' to assess response bias) in a staging system for a clinically distinct, 'visuospatial' dementia (posterior cortical atrophy) [12]:…”

COS-PPA: protocol to develop a core outcome set for primary progressive aphasia

“…18 Additionally, given the heterogeneity of PPA, a COS should include consideration of the value of different outcomes for different PPA syndromes. 19 We have no roadmap at present for determining or evaluating intervention outcomes in PPA and it presents radically different challenges to stroke aphasia (the current standard for aphasia interventions)-both due to its intrinsically progressive nature and also because it entails significant issues with non-verbal cognition and behaviour over the course of the illness that interacts with communication functionthus, there is a fundamental need to reorient researchers and clinicians to PPA. [18][19][20] In summary, there is a need for a specific COS, that details key measures addressing the needs of people with PPA.…”

The Functional Communication Checklist for People Living with Primary Progressive Aphasia: Study Protocol

“…PPA causes important changes in functional communication (FC), which is defined as the "transactional success" of expression [6], and which is a fundamental feature of human connection [7]. FC ability in PPA diverges by variant, individual differences, and time [5,[8][9][10]. A person-centered approach-a holistic and humanistic method that promotes the autonomy and needs of the patient-is integral to establish how individual differences can impact a person's success in FC [9,11] and to deliver individualized care [9,12].…”