Classification of the primary progressive aphasias: principles and review of progress since 2011

Highly influential recommendations published in 2011 for the classification of the primary progressive aphasias (PPA) distinguished three subtypes: the semantic variant, the nonfluent/agrammatic variant, and the logopenic variant. We review empirical evidence published after 2011 that bears relevance to the validity of the recommended classification scheme. The studies that we review principally rely on monocentric, memory clinic-based consecutive series of PPA patients. We review whether a data-driven analysis of neurolinguistic test scores confirms the subtyping that was based on expert consensus, whether the 2011 subtyping covers the diversity of PPA in a comprehensive manner, and whether the proposed subgroups differ along dimensions that are not explicitly part of the defining criteria, such as diffusion tractography. Data-driven mathematical analyses of neurolinguistic data in PPA broadly confirm the presence of separate clusters corresponding to the subtypes but also leave 15-30 % unclassified. A comprehensive description of PPA requires the addition of the mixed variant as a fourth subtype and needs to leave room for cases fulfilling the criteria for a root diagnosis of PPA but not those of any of the three subtypes. Finally, given the limited predictive value of the clinical phenotype for the underlying neuropathology, biomarkers of the underlying pathology are likely of clinical utility in PPA.