title: How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease.
abstract: The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington's disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington's Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington's Disease (RIL-HD). All were assessed with the Unified Huntington's Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required.
authors.affiliation: INSERM U955 E01, Neuropsychologie interventionnelle, Institut Mondor de Recherche Biomédicale, Créteil, France.|INSERM UMRS1138 E22, Science de l'information au service de la médecine personnalisée, Centre de Recherche des Cordeliers, Université Paris 5, Université Paris 6, Paris, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|Ecole Normale Supérieure, Institut d'Etude de la Cognition, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schramm
authors.affiliation: INSERM UMRS1138 E22, Science de l'information au service de la médecine personnalisée, Centre de Recherche des Cordeliers, Université Paris 5, Université Paris 6, Paris, France.|Assistance Publique-Hôpitaux de Paris, Service d'informatique et statistiques, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Katsahian
authors.affiliation: INSERM U955 E01, Neuropsychologie interventionnelle, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|Ecole Normale Supérieure, Institut d'Etude de la Cognition, Paris, France.|Assistance Publique-Hôpitaux de Paris, Centre National de Référence pour la Maladie de Huntington, Hôpital Henri Mondor, Créteil, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Youssov
authors.affiliation: Leenaards Memory Centre, Clinical Neurosciences Department, CHUV Lausanne, Lausanne, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Démonet
authors.affiliation: Centre Hospitalier Universitaire d'Amiens, Service de neurologie, Amiens, France.|EA 4559 - Laboratoire de Neurosciences Fonctionnelles et Pathologie (LNFP), Université de Picardie Jules Verne (UPJV), Amiens, France.|SFR CAP-Santé (FED 4231), Amiens, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Krystkowiak
authors.affiliation: Hôpital Erasme ULB, Service de Neurologie, Bruxelles, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Supiot
authors.affiliation: CHU d'Angers, Centre de Référence des Maladies Neurogénétiques, Service de Neurologie, Angers, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.affiliation: INSERM U955 E01, Neuropsychologie interventionnelle, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|Ecole Normale Supérieure, Institut d'Etude de la Cognition, Paris, France.|Assistance Publique-Hôpitaux de Paris, Centre National de Référence pour la Maladie de Huntington, Hôpital Henri Mondor, Créteil, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cleret de Langavant
authors.affiliation: INSERM U955 E01, Neuropsychologie interventionnelle, Institut Mondor de Recherche Biomédicale, Créteil, France.|Université Paris Est, Faculté de Médecine, Créteil, France.|Ecole Normale Supérieure, Institut d'Etude de la Cognition, Paris, France.|Assistance Publique-Hôpitaux de Paris, Centre National de Référence pour la Maladie de Huntington, Hôpital Henri Mondor, Créteil, France.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Bachoud-Lévi
mesh_terms: D000328:Adult; D000465:Algorithms; D003071:Cognition; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015203:Reproducibility of Results