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Background: Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients., Methods: Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry., Results: sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant right ATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants., Conclusion: We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD., (© 2024. The Author(s).)

Objective: The hexanucleotide repeat expansion in C9orf72 is an associated genetic cause in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the "ALS/FTD" spectrum prevails clinical heterogeneity and an in vivo knowledge of the underling brain dysfunction in patients carrying C9orf72 mutation remain limited and only described at group level. The study aimed to assess the brain metabolic alterations characterizing patients with C9orf72 mutation using FDG-PET in single individuals., Methods: We applied a validated statistical parametric mapping (SPM) voxel-based procedure for FDG-PET data to obtain maps of brain relative hypometabolism and hypermetabolism at single-subject level in six FTD/ALS patients carrying the C9orf72 mutation., Results: Clinical diagnoses classified the patients as right semantic variant of frontotemporal dementia (one case, C9svFTD), behavioral variant of frontotemporal dementia (two cases, C9bvFTD), and bulbar amyotrophic lateral sclerosis (three cases, C9bALS). The FDG-PET SPM revealed a prevalent frontal hypometabolism in C9bvFTD cases, and right temporal polar and lateral involvement in C9svFTD, consistent with the clinical diagnosis. There was a quite comparable occipital and cerebellar hypermetabolism in these cases. The three C9bALS patients showed variable patterns of hypo- and hypermetabolism., Conclusions: The present work is the first in vivo FDG-PET study showing the heterogeneous patterns of brain regional hypo- and hypermetabolism in single patients sharing C9orf72 mutation. Brain hypometabolism was consistent with the clinical phenotypes, supporting the diagnostic importance of neuroimaging functional biomarkers to capture at single-subject level specific brain dysfunction.