| Title: |
Cognitive composites for genetic frontotemporal dementia: GENFI-Cog |
| Authors: |
Poos, JM; Moore, KM; Nicholas, J; Russell, LL; Peakman, G; Convery, RS; Jiskoot, LC; van der Ende, E; van den Berg, E; Papma, JM; Seelaar, H; Pijnenburg, YAL; Moreno, F; Sanchez-Valle, R; Borroni, B; Laforce, R; Masellis, M; Tartaglia, C; Graff, C; Galimberti, D; Rowe, JB; Finger, E; Synofzik, M; Vandenberghe, R; de Mendonça, A; Tiraboschi, P; Santana, I; Ducharme, S; Butler, C; Gerhard, A; Levin, J; Danek, A; Otto, M; Le Ber, I; Pasquier, F; van Swieten, JC; Rohrer, JD; Bouzigues, A; Rossor, MN; Fox, NC; Warren, JD; Bocchetta, M; Swift, IJ; Shafei, R; Heller, C; Todd, E; Cash, D; Woollacott, I; Zetterberg, H; Nelson, A; Guerreiro, R; Bras, J; Thomas, DL; Mead, S; Meeter, L; Panman, J; van Minkelen, R; Barandiaran, M; Indakoetxea, B; Gabilondo, A; Tainta, M; Gorostidi, A; Zulaica, M; Díez, A; Villanua, J; Borrego-Ecija, S; Olives, J; Lladó, A; Balasa, M; Antonell, A; Bargallo, N; Premi, E; Gazzina, S; Gasparotti, R; Archetti, S; Black, S; Mitchell, S; Rogaeva, E; Freedman, M; Keren, R; Tang-Wai, D; Thonberg, H; Öijerstedt, L; Andersson, C; Jelic, V; Arighi, A; Fenoglio, C; Scarpini, E; Fumagalli, G; Cope, T; Timberlake, C; Rittman, T; Shoesmith, C; Bartha, R; Rademakers, R; Wilke, C; Karnarth, H-O; Bender, B; Bruffaerts, R; Vandamme, P; Vandenbulcke, M; Ferreira, CB; Miltenberger, G; Maruta, C; Verdelho, A; Afonso, S; Taipa, R; Caroppo, P; Di Fede, G; Giaccone, G; Prioni, S; Redaelli, V; Rossi, G; Duro, D; Almeida, MR; Castelo-Branco, M; Leitão, MJ; Tabuas-Pereira, M; Santiago, B; Gauthier, S; Rosa-Neto, P; Veldsman, M; Thompson, P; Langheinrich, T; Prix, C; Hoegen, T; Wlasich, E; Loosli, S; Schonecker, S; Anderl-Straub, S; Lombardi, J; Bargalló, N; Benussi, A; Cantoni, V; Bertoux, M; Bertrand, A; Brice, A; Camuzat, A; Colliot, O; Sayah, S; Funkiewiez, A; Rinaldi, D; Lombardi, G; Nacmias, B; Saracino, D; Bessi, V; Ferrari, C; Cañada, M; Deramecourt, V; Kuchcinski, G; Lebouvier, T; Ourselin, S; Polito, C; Rollin, A |
| Source: |
Alzheimer's Research & Therapy , 14 (1) , Article 10. (2022) |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Frontotemporal dementia; Cognition; Neuropsychology; Composite score; Language; Attention; Executive function; Memory; Social cognition |
| Description: |
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 regression 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 theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10142288/1/Poos,ALZ2022.pdf; https://discovery.ucl.ac.uk/id/eprint/10142288/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10142288/1/Poos,ALZ2022.pdf; https://discovery.ucl.ac.uk/id/eprint/10142288/ |
| Rights: |
open |
| Accession Number: |
edsbas.F8EDC11 |
| Database: |
BASE |