Cross-linguistic and neuropsychological considerations in diagnosing mixed variant of primary progressive aphasia: a narrative review

Background/aims Primary progressive aphasia (PPA) encompasses a group of neurodegenerative disorders characterized by progressive language decline. However, diagnosing mixed variant of PPA (mvPPA) can be challenging because symptoms overlap across PPA subtypes. This ambiguity is further compounded by cross-linguistic variations in language function and the limited availability of diagnostic tools for languages other than English. This study bridges a critical gap in the field by providing the first review regarding mvPPA from both neuropsychological and cross-linguistic perspectives.Methods/procedures This narrative review examined studies from four databases: MEDLINE, Web of Science, Google Scholar, and Scopus, spanning the period from 2000 to 2024. A summary of the core clinical and neuropsychological features of different PPA subtypes, along with their corresponding clinical characteristics, is presented for the selected studies.Results/outcomes Eighteen selected studies included patients with mixed PPA variant. These patients were heterogeneous, with complex neuropsychological profiles that combine features of established PPA variants. Neuropsychological findings showed heterogeneous profiles in mixed PPA. Naming impairments, grammatical errors, and phonological difficulties were common. This stage of disease evolves from the spread of atrophy and mixed pathology, but it can also emerge earlier. Neuroimaging findings, such as atrophy and hypoperfusion on MRI and PET scans, were sometimes inconsistent with clinical diagnoses.Conclusion Diagnosing mixed variant of PPA presents significant challenges. There are considerable gaps in our understanding of how language background, neuroimaging markers, and neuropsychological functions interact in clinical and cross-linguistic manifestations. Urgent cross-linguistic research is needed, especially for bilingual or multilingual individuals with PPA, to better characterize linguistic typologies and shared brain atrophy sites across language systems.