Title :

Cognitive composites for genetic frontotemporal dementia: GENFI-Cog.

Author(s) :

Poos, J. M. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
National Hospital for Neurology and Neurosurgery [NHNN]
Moore, K. M. [Auteur]
National Hospital for Neurology and Neurosurgery [NHNN]
Nicholas, J. [Auteur]
London School of Hygiene and Tropical Medicine [LSHTM]
Russell, L. L. [Auteur]
UCL Institute of Neurology, Queen Square [London]
Peakman, G. [Auteur]
UCL Institute of Neurology, Queen Square [London]
Convery, R. S. [Auteur]
UCL Institute of Neurology, Queen Square [London]
Jiskoot, L. C. [Auteur]
UCL Institute of Neurology, Queen Square [London]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Van Der Ende, E. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Van Den Berg, E. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Papma, J. M. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Seelaar, H. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Pijnenburg, Y. A. L. [Auteur]
Amsterdam University Medical Centers [Amsterdam UMC]
Moreno, F. [Auteur]
Hospital Universitario Donostia [San Sebastian, Spain] [HUD]
Sanchez-Valle, R. [Auteur]
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Borroni, B. [Auteur]
Università degli Studi di Brescia = University of Brescia [UniBs]
Laforce, R. [Auteur]
CHU de Québec–Université Laval
Masellis, M. [Auteur]
University of Toronto
Tartaglia, C. [Auteur]
Toronto Western Hospital
Graff, C. [Auteur]
Karolinska University Hospital [Stockholm]
Galimberti, D. [Auteur]
Università degli Studi di Milano = University of Milan [UNIMI]
Rowe, J. B. [Auteur]
University of Cambridge [UK] [CAM]
Finger, E. [Auteur]
University of Western Ontario [UWO]
Synofzik, M. [Auteur]
Eberhard Karls Universität Tübingen = University of Tübingen
Vandenberghe, R. [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
De Mendonça, A. [Auteur]
Universidade de Lisboa = University of Lisbon = Université de Lisbonne [ULISBOA]
Tiraboschi, P. [Auteur]
Fondazione IRCCS Istituto Neurologico "Carlo Besta"
Santana, I. [Auteur]
Centro Hospitalar e Universitário [Coimbra]
Ducharme, S. [Auteur]
McGill University = Université McGill [Montréal, Canada]
Butler, C. [Auteur]
University of Oxford
Gerhard, A. [Auteur]
University of Manchester [Manchester]
Levin, J. [Auteur]
Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München [LMU]
Danek, A. [Auteur]
Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München [LMU]
Otto, M. [Auteur]
Universitätsklinikum Ulm - University Hospital of Ulm
Le Ber, I. [Auteur]
CHU Pitié-Salpêtrière [AP-HP]
Institut du Cerveau = Paris Brain Institute [ICM]
Pasquier, Florence [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Van Swieten, J. C. [Auteur]
Erasmus University Medical Center [Rotterdam] [Erasmus MC]
Rohrer, J. D. [Auteur]
UCL Institute of Neurology, Queen Square [London]

Journal title :

Alzheimers Res Ther

Volume number :

14

Pages :

10

Publication date :

2022-01-21

ISSN :

1758-9193

English keyword(s) :

Frontotemporal dementia
Cognition
Neuropsychology
Composite score
Language
Attention
Executive function
Memory
Social cognition

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Poos et al. Alzheimer’s Research & Therapy (2022) 14:10 https://doi.org/10.1186/s13195-022-00958-0 RESEARCH Cognitive composites for genetic frontotemporal dementia: GENFI-Cog Jackie M. Poos 1,2 , Katrina M. Moore2 , ...
Show more >Poos et al. Alzheimer’s Research & Therapy (2022) 14:10 https://doi.org/10.1186/s13195-022-00958-0 RESEARCH Cognitive composites for genetic frontotemporal dementia: GENFI-Cog Jackie M. Poos 1,2 , Katrina M. Moore2 , Jennifer Nicholas3 , Lucy L. Russell2 , Georgia Peakman2 , Rhian S. Convery2 , Lize C. Jiskoot1,2 , Emma van der Ende1 , Esther van den Berg1 , Janne M. Papma1 , Harro Seelaar1 , Yolande A. L. Pijnenburg 4 , Fermin Moreno 5 , Raquel Sanchez‑Valle6 , Barbara Borroni7 , Robert Laforce8 , Mario Masellis9 , Carmela Tartaglia10 , Caroline Graff11 , Daniela Galimberti12,13 , James B. Rowe14 , Elizabeth Finger 15 , Matthis Synofzik16,17 , Rik Vandenberghe18 , Alexandre de Mendonça19 , Pietro Tiraboschi20 , Isabel Santana21 , Simon Ducharme22 , Chris Butler23 , Alexander Gerhard24 , Johannes Levin 25,26,27 , Adrian Danek25 , Markus Otto28 , Isabel Le Ber29,30,31 , Florence Pasquier32,33,34 , John C. van Swieten1 , Jonathan D. Rohrer 2* and on behalf of the Genetic FTD Initiative (GENFI) Abstract Background: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. Methods: A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR® plus NACC‑FTLD ≥ 0.5 and 275 controls. Logistic regres‑ sion was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theo‑ retical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC‑FTLD 0.5) to a fully sympto‑ matic stage (CDR® plus NACC‑FTLD ≥ 1). Time‑to‑event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC‑FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be). Results: The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan‑Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC‑FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period. Discussion: We created gene‑specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitiveShow less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Troubles cognitifs dégénératifs et vasculaires

Submission date :

2024-01-16T01:34:19Z
2025-02-26T08:15:01Z