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Unifying Divergent Conceptions in Nonfluent/Agrammatic and Semantic Primary Progressive Aphasia.

Marc Teichmann1, Kimihiro Nakamura2

  • 1French Reference Center for 'Rare or Early Onset Dementias', Institute of Memory and Alzheimer's Disease, Department of Neurology, Pitié-Salpêtrière University Hospital, AP-HP, 47-83 boulevard de l'Hôpital, 75013 Paris, France.

Brain Sciences
|May 27, 2026
PubMed
Summary

This review addresses diagnostic challenges in primary progressive aphasia variants. It proposes integrated frameworks for nonfluent/agrammatic PPA and semantic PPA, suggesting continuums of impairment.

Keywords:
languageprimary progressive aphasiaprimary progressive apraxia of speech

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Area of Science:

  • Neuroscience
  • Linguistics
  • Neurology

Background:

  • Primary progressive aphasia (PPA) presents diagnostic challenges, particularly differentiating nonfluent/agrammatic PPA (nfav-PPA) from primary progressive apraxia of speech (PPAOS).
  • Existing diagnostic criteria for PPA have absorbed semantic dementia (SD) into semantic variant PPA (sv-PPA), leaving other semantic phenotypes unclassified.
  • There is a need for validated clinical tools to assess apraxia of speech and syntactic/semantic abilities.

Purpose of the Study:

  • To review and reconcile divergent conceptions of nfav-PPA/PPAOS and sv-PPA/SD.
  • To propose integrated conceptual frameworks for these PPA variants based on clinical, neurocognitive, and neurobiological data.
  • To suggest graded continuums of impairment for both nfav-PPA/PPAOS and semantic variants of PPA.

Main Methods:

  • Narrative review of clinical, neurocognitive, and neurobiological literature.
  • Analysis of diagnostic controversies in nfav-PPA/PPAOS and sv-PPA/SD.
  • Development of conceptual-integrative models for PPA classification.

Main Results:

  • A proposed framework integrates nfav-PPA and PPAOS into a graded continuum from syntactic to phonetic-articulatory impairments.
  • A second proposed model integrates sv-PPA and SD, suggesting a continuum from verbal to non-verbal semantic impairments, including social-semantic phenotypes.
  • The frameworks aim to resolve diagnostic controversies and accommodate a wider range of PPA presentations.

Conclusions:

  • Integrated frameworks can resolve diagnostic controversies in primary progressive aphasia.
  • Recognizing continuums of impairment is crucial for accurate classification and understanding of PPA subtypes.
  • Further research and validated tools are needed to refine the diagnosis and management of PPA.