FDG-PET in the Evaluation of Primary Progressive Aphasia: A Narrative Review

Background and Objectives: Primary progressive aphasia (PPA) and its variants-logopenic (lvPPA), semantic (svPPA), and nonfluent/agrammatic (nfvPPA)-are progressive neurocognitive syndromes characterized by predominant language impairment and associated with heterogeneous underlying neuropathologies. Accurate diagnosis remains challenging due to overlapping clinical features and complex pathobiological mechanisms. Fluorodeoxyglucose positron emission tomography (FDG-PET), which reflects regional cerebral glucose metabolism, may provide valuable insights into both the diagnosis and pathophysiological characterization of PPA. Materials and Methods: We reviewed the current literature and identified 48 original research articles that utilized FDG-PET in the evaluation of at least one PPA variant. Eight studies focused exclusively on lvPPA, six on svPPA, and two on nfvPPA, either alone or in comparison with other neurodegenerative diseases. Eighteen studies evaluated at least two PPA variants, while thirteen compared multiple PPA variants with other neurodegenerative disorders. Results: Most studies identified characteristic hypometabolic patterns for each PPA variant: left temporoparietal regions in lvPPA, bilateral anterior temporal regions with left predominance in svPPA, and left posterior frontal regions in nfvPPA. These variant-specific metabolic signatures may support differential diagnosis. Additionally, FDG-PET provided important insights into disease progression, including associations with worsening language impairment, evolution toward broader neurodegenerative syndromes, and correlations with specific neurocognitive deficits. These findings are largely consistent with other neuroimaging modalities and disease-specific biomarkers. However, limitations such as small sample sizes and the lack of autopsy confirmation in most studies limit the robustness of the results. Conclusions: FDG-PET appears to be a valuable tool for the diagnosis, differential diagnosis, and pathophysiological understanding of PPA. Nevertheless, large-scale, multicenter investigations incorporating pathologically confirmed cases to further validate its clinical utility are needed.