Subtyping mixed primary progressive aphasia

Salvatore Mazzeo, MD, PhD, Vita-Salute San Raffaele University, Milan & AOU Careggi, Florence, Italy, summarizes the findings of a study exploring the phenotypic classification of primary progressive aphasia (PPA), to identify mixed phenotypes combining the canonical nonfluent/aggramatic (nfvPPA), semantic (svPPA), and logopenic (lvPPA) PPA variants. These three variant syndromes have been codified in 2011 international diagnostic consensus criteria to reliably guide current diagnostic procedures. However, atypical cases are common, with patients presenting a mixed PPA phenotype. This study identified several phenotypic classifications within a mixed PPA population, including presentation combining lvPPA and svPPA variants. Interestingly, a cluster of patients within the s/lvPPA group displayed an Alzheimer’s disease-like biomarker profile, indicating that a subgroup of s/lvPPA may represent a clinical manifestation of AD-related PPA. Accordingly, further confirmation of this diagnostic overlap may indicate that mixed PPA patients should not be excluded from future research on the efficacy of AD disease-modifying therapies, particularly as the proportion of patients with a mixed presentation is increasing. This interview took place at the AD/PD™ 2024 congress in Lisbon, Portugal.

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