Publication Date

3-7-2024

Journal

Alzheimer's Research & Therapy

DOI

10.1186/s13195-024-01403-0

PMID

38448894

PMCID

PMC10918940

PubMedCentral® Posted Date

3-7-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Semantics, Multidimensional Scaling Analysis, Linguistics, Fluorodeoxyglucose F18, Memory Disorders, Aphasia, Primary Progressive, Logopenic PPA, Semantic PPA, Lexico-semantics, Phonology, Verbal working memory, Profile Analysis via Multidimensional Scaling, FDG-PET

Abstract

BACKGROUND: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce.

METHODS: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [

RESULTS: Patients' profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space.

DISCUSSION: Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups.

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