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  -