Clinical and Neuroanatomical Characterization of the Semantic Behavioural Variant of Frontotemporal Dementia in a Multicentre Italian Cohort
Alma Ghirelli1, Edoardo Spinelli1, Elisa Canu4, Silvia Basaia4, Veronica Castelnovo4, Giordano Cecchetti2, Elisa Sibilla4, Giuseppe Magnani5, Francesca Caso5, Paola Caroppo6, Sara Prioni6, Cristina Villa6, Lucio Tremolizzo7, Ildebrando Appollonio7, Federico Verde8, Nicola Ticozzi8, Vincenzo Silani8, Massimo Filippi3, Federica Agosta1
1Neuroiaging Research Unit, Division of Neuroscience; and Neurology Unit, 2Neuroiaging Research Unit, Division of Neuroscience; Neurology Unit; and Neurophysiology Service, 3Neuroiaging Research Unit, Division of Neuroscience; Neurology Unit; Neurorehabilitation Unit; and Neurophysiology Service, IRCSS San Raffaele Scientific Institute; and Vita-Salute San Raffaele University, 4Neuroiaging Research Unit, Division of Neuroscience, 5Neurology Unit, IRCSS San Raffaele Scientific Institute, 6Unit of Neurology 5 – Neuropathology, Fondazione IRCSS Istituto Neurologico Carlo Besta, 7Neurology Unit, “San Gerardo” Hospital and University of Milano-Bicocca, 8Department of Neurology and Laboratory of Neuroscience; and “Dino Ferrari” Center, Department of Pathophysiology and Transplantation, IRCCS Istituto Auxologico Italiano, and Università degli Studi di Milano
Objective:
To evaluate clinical, neuropsychological, neuroimaging and genetic features of an Italian cohort of semantic behavioral variant FTD (sbvFTD) patients, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients.
Background:
sbvFTD is a recently recognized neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL).
Design/Methods:
Fifteen sbvFTD, 63 bvFTD and 25 svPPA patients and forty age- and sex-matched controls were enrolled. Patients underwent clinical and cognitive evaluations and brain MRI on a 3T scanner. Emerging symptoms of sbvFTD patients were recorded. Grey matter atrophy was investigated using voxel-based morphometry.
Results:
Age at onset and disease duration were comparable among groups. The majority of sbvFTD patients developed early person-specific semantic knowledge loss and words (67%), objects semantic loss (67%), complex compulsions and rigid thought process (60%). As the disease unfolded, more behavioral symptoms emerged (apathy/inertia, loss of empathy, anxiety, suspiciousness). sbvFTD patients showed sparing of attentive and executive functions, especially compared to bvFTD and better visual naming and semantic fluency 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 a pattern of predominant right ATL atrophy, almost specular to the left-sided pattern of atrophy of svPPA. Three sbvFTD patients presented pathogenic genetic variants (n=1 C9orf72, n=1 MAPT, n=1 GRN).
Conclusions:
We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of two out of three core diagnostic criteria (person-specific semantic knowledge loss, mental rigidity and loss of empathy), along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes should prompt a diagnosis of sbvFTD.