TY - JOUR PB - Wiley VL - 8 JF - Alzheimer's & Dementia: Translational Research & Clinical Interventions N1 - © 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/). TI - Differences and similarities between familial and sporadic frontotemporal dementia: An Italian single-center cohort study Y1 - 2022/// UR - https://discovery.ucl.ac.uk/id/eprint/10153550/ ID - discovery10153550 AV - public IS - 1 N2 - INTRODUCTION: The possibility to generalize our understandings on treatments and assessments to both familial frontotemporal dementia (f-FTD) and sporadic FTD (s-FTD) is a fundamental perspective for the near future, considering the constant advancement in potential disease-modifying therapies that target particular genetic forms of FTD. We aimed to investigate differences in clinical features, cerebrospinal fluid (CSF), and blood-based biomarkers between f-FTD and s-FTD. METHODS: In this longitudinal cohort study, we evaluated a consecutive sample of symptomatic FTD patients, classified as f-FTD and s-FTD according to Goldman scores (GS). All patients underwent clinical, behavioral, and neuropsychiatric symptom assessment, CSF biomarkers and serum neurofilament light (NfL) analysis, and brain atrophy evaluation with magnetic resonance imaging. RESULTS: Of 570 patients with FTD, 123 were classified as f-FTD, and 447 as s-FTD. In the f-FTD group, 95 had a pathogenic FTD mutation while 28 were classified as GS = 1 or 2; of the s-FTD group, 133 were classified as GS = 3 and 314 with GS = 4. f-FTD and s-FTD cases showed comparable demographic features, except for younger age at disease onset, age at diagnosis, and higher years of education in the f-FTD group (all P < .05). f-FTD showed worse behavioral disturbances as measured with Frontal Behavioral Inventory (FBI) negative behaviors (14.0 ± 7.6 vs. 11.6 ± 7.4, P = .002), and positive behaviors (20.0 ± 11.0 vs. 17.4 ± 11.8, P = .031). Serum NfL concentrations were higher in patients with f-FTD (70.9 ± 37.9 pg/mL) compared to s-FTD patients (37.3 ± 24.2 pg/mL, P < .001), and f-FTD showed greater brain atrophy in the frontal and temporal regions and basal ganglia. Patients with f-FTD had significantly shorter survival than those with s-FTD (P = .004). DISCUSSION: f-FTD and s-FTD are very similar clinical entities, but with different biological mechanisms, and different rates of progression. The parallel characterization of both f-FTD and s-FTD will improve our understanding of the disease, and aid in designing future clinical trials for both genetic and sporadic forms of FTD. KW - C9orf72 KW - GRN KW - familial KW - frontotemporal dementia KW - genetic KW - sporadic A1 - Benussi, Alberto A1 - Libri, Ilenia A1 - Premi, Enrico A1 - Alberici, Antonella A1 - Cantoni, Valentina A1 - Gadola, Yasmine A1 - Rivolta, Jasmine A1 - Pengo, Marta A1 - Gazzina, Stefano A1 - Calhoun, Vince D A1 - Gasparotti, Roberto A1 - Zetterberg, Henrik A1 - Ashton, Nicholas J A1 - Blennow, Kaj A1 - Padovani, Alessandro A1 - Borroni, Barbara ER -