Brain 18F-FDG PET/CT usefulness in primary progressive aphasia variant diagnosis and in their development into Alzheimer’s disease or fronto-temporal dementia

Background-Aim: Primary Progressive Aphasia (PPA) is a heterogeneous clinical entity that includes different variants such as Logopenic Aphasia (LPA) that could develop into Alzheimer’s disease (AD) and Progressive Non-Fluent Aphasia (PNFA) variant and Semantic Variant (SV) that could develop into Fronto-Temporal Dementia (FTD). We investigated brain 18F-FDG PET/CT usefulness in patients with uncertain PPA diagnosis and in those with already ascertained diagnosis to evaluate a possible early development into AD or FTD. Methods: We retrospectively enrolled 49 consecutive patients: 15 cases with uncertain symptoms attributable to PPA variants of recent appearance (Group A) and 34 with PPA already ascertained with suspicious clinical signs for early development into AD or FTD (Group B). All patients underwent PET/CT after i.v. injection of 370 MBq dose of 18F-FDG using a Discovery tomograph (GE). Images were analyzed both qualitatively (QL) and quantitatively (QN), the latter by an automated software (Cortex ID, GE Healthcare, USA) that produces brain metabolic map compared with normal age matched controls. Results: QL and QN analyses of PET/CT showed different patterns of cortical hypometabolism in the two Groups of patients. In particular, in Group A, 8/15 patients showed a selective hypometabolism in fronto-temporal and fronto-parietal regions (6 bilateral and 2 in left hemisphere) and were classified as PNFA and SV variants, respectively. In 5/15 cases hypometabolic areas were detected in temporoparietal regions (3 bilaterally and 2 in left hemisphere), in 1/15 cases in right temporo-parietal regions with the patients classified as affected by LPA variant, while hypometabolism was diffuse in the remaining 1/15 cases. QN analysis could better discriminate the areas of bilateral hypometabolism including the apparent diffuse hypometabolism evidenced at QL in one case; thus, 9/15 patients were classified as at higher risk of early progressing into AD (6 cases) or FTD (3 cases), confirming the initial suspect clinical symptoms of disease. In 18/34 Group B cases, PET/CT evidenced areas of hypometabolism in fronto-temporal and fronto-parietal regions (14 bilateral and 4 in left hemisphere) and the classification in PNFA and SV patients was confirmed, while the 13/34 cases with reduced FDG uptake in temporo-parietal regions (8 bilateral, 3 in left and 2 in right hemispheres) were classified as LPA variant. Considering the data of QN analysis, 22/31 (71%) cases showed a considerable hypometabolism in bilateral brain areas and were classified as high risk of progressing into AD ( 8 cases) or FTD (14 cases). Moreover, in the 2/34 cases with diffuse hypometabolism the diagnosis was uncertain also at QN analysis as well as in the remaining case in whom FDG uptake was apparently normal despite suspect symptoms of disease. Conclusions: 18F-FDG PET/CT proved a valuable diagnostic tool to give a useful support for PPA variant diagnosis and for establishing the development of PPA into FTD or AD in both recent and advanced stage of diseases with QN analysis representing the best methods to reach the diagnosis. However, the finding of diffuse hypometabolism in two cases and normal cortical FDG uptake in one case despite the symptoms of PPA remains to clarify with a close follow up. A larger number of cases and a longer follow up is necessary to confirm the present data