The Role of Single-Subject Brain Metabolic Patterns in the Early Differential Diagnosis of Primary Progressive Aphasias and in Prediction of Progression to Dementia.
Primary progressive aphasia (PPA) is a clinical syndrome due to different neurodegenerative conditions in which an accurate early diagnosis needs to be supported by a reliable diagnostic tool at the individual level. In this study, we investigated in PPA the FDG-PET brain metabolic patterns at the single-subject level, in order to assess the case-to-case variability and its relationship with clinical-neuropsychological findings.



55 patients (i.e., 11 semantic variant/sv-PPA, 19 non fluent variant/nfv-PPA, 17 logopenic variant/lv-PPA, 3 slowly progressive anarthria/SPA, and 5 mixed PPA/m-PPA) were included. Clinical-neuropsychological information and FDG-PET data were acquired at baseline. A follow-up of 27.4±12.55 months evaluated the clinical progression. Brain metabolism was analyzed using an optimized and validated voxel-based SPM method at the single-subject level.



FDG-PET voxel-wise metabolic assessment revealed specific metabolic signatures characterizing each PPA variant at the individual level, reflecting the underlying neurodegeneration in language networks. Notably, additional dysfunctional patterns predicted clinical progression to specific dementia conditions. In the case of nfv-PPA, a metabolic pattern characterized by involvement of parietal, subcortical and brainstem structures predicted progression to a corticobasal degeneration syndrome or to progressive supranuclear palsy. lv-PPA and sv-PPA cases who progressed to Alzheimer's disease and frontotemporal dementia at the follow-up presented with extended bilateral patterns at baseline.



Our results indicate that FDG-PET voxel-wise imaging is a valid biomarker for the early differential diagnosis of PPAs and for the prediction of progression to specific dementia condition. This study supports the use of FDG-PET imaging quantitative assessment in clinical settings for a better characterization of PPA individuals and prognostic definition of possible endo-phenotypes.
Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Department of Clinical Neuroscience, San Raffaele Turro Hospital, Milan, Italy.
Chiara
C
Cerami
Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Alessandra
A
Dodich
Vita-Salute San Raffaele University, Milan, Italy.
Lucia
L
Greco
Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Department of Clinical Neuroscience, San Raffaele Turro Hospital, Milan, Italy.
Sandro
S
Iannaccone
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Giuseppe
G
Magnani
Department of Clinical Neuroscience, San Raffaele Turro Hospital, Milan, Italy.
Alessandra
A
Marcone
Department of Clinical Neuroscience, San Raffaele Turro Hospital, Milan, Italy.
Elisabetta
E
Pelagallo
Department of Neurology, San Raffaele Hospital, Milan, Italy.
Roberto
R
Santangelo
Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|NEtS Center, Istituto Universitario di Studi Superiori, Pavia, Italy.
Stefano F
SF
Cappa
Vita-Salute San Raffaele University, Milan, Italy.|Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Department of Nuclear Medicine, San Raffaele Hospital, Milan, Italy.
Daniela
D
Perani
D000368:Aged; D018888:Aphasia, Primary Progressive / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003071:Cognition; D003704:Dementia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003937:Diagnosis, Differential; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D057285:Precision Medicine; D019275:Radiopharmaceuticals; D012189:Retrospective Studies
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
FDG-PET; logopenic variant of primary progressive aphasia; non fluent variant of primary progressive aphasia; positron emission tomography; primary progressive aphasia; semantic variant of primary progressive aphasia
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