학술논문
Cognitive impact of multidomain intervention and omega 3 according to blood A[beta]42/40 ratio: a subgroup analysis from the randomized MAPT trial
Document Type
Report
Author
Delrieu, Julien; Vellas, Bruno; Guyonnet, Sophie; Cantet, Christelle; Ovod, Vitaliy; Li, Yan; Bollinger, James; Bateman, Randall; Andrieu, Sandrine; Carrié, Isabelle; Brigitte, Lauréane; Faisant, Catherine; Lala, Françoise; Villars, Hélène; Combrouze, Emeline; Badufle, Carole; Zueras, Audrey; Morin, Christophe; Van Kan, Gabor Abellan; Dupuy, Charlotte; Rolland, Yves; Caillaud, Céline; Ousset, Pierre-Jean; Willis, Sherry; Belleville, Sylvie; Gilbert, Brigitte; Fontaine, Francine; Dartigues, Jean-François; Marcet, Isabelle; Delva, Fleur; Foubert, Alexandra; Cerda, Sandrine; Costes, Corinne; Rouaud, Olivier; Manckoundia, Patrick; Quipourt, Valérie; Marilier, Sophie; Franon, Evelyne; Bories, Lawrence; Pader, Marie-Laure; Basset, Marie-France; Lapoujade, Bruno; Faure, Valérie; Tong, Michael Li Yung; Malick-Loiseau, Christine; Cazaban-Campistron, Evelyne; Desclaux, Françoise; Blatge, Colette; Dantoine, Thierry; Laubarie-Mouret, Cécile; Saulnier, Isabelle; Clément, Jean-Pierre; Picat, Marie-Agnès; Bernard-Bourzeix, Laurence; Willebois, Stéphanie; Désormais, Iléana; Cardinaud, Noëlle; Bonnefoy, Marc; Livet, Pierre; Rebaudet, Pascale; Gédéon, Claire; Burdet, Catherine; Terracol, Flavien; Pesce, Alain; Roth, Stéphanie; Chaillou, Sylvie; Louchart, Sandrine; Sudres, Kristel; Lebrun, Nicolas; Barro-Belaygues, Nadège; Touchon, Jacques; Bennys, Karim; Gabelle, Audrey; Romano, Aurélia; Touati, Lynda; Marelli, Cécilia; Pays, Cécile; Robert, Philippe; Le Duff, Franck; Gervais, Claire; Gonfrier, Sébastien; Gasnier, Yannick; Bordes, Serge; Begorre, Danièle; Carpuat, Christian; Khales, Khaled; Lefebvre, Jean-François; El Idrissi, Samira Misbah; Skolil, Pierre; Salles, Jean-Pierre; Coley, Nicola
Source
Alzheimer's Research & Therapy. October 23, 2023, Vol. 15 Issue 1
Subject
Language
English
ISSN
1758-9193
Abstract
Background In MAPT (Multidomain Alzheimer Preventive Trial), a cognitive effect of multidomain intervention (MI) was showed in non-demented subjects with positive amyloid PET. However, screening eligible patients for multidomain intervention by PET is difficult to generalize in real-world settings. Methods MAPT study was a 3-year, randomized, placebo-controlled trial followed by a 2-year observational and optional extension. All participants were non-demented and randomly assigned (1:1:1:1) to the MI plus omega 3, MI plus placebo, omega 3 alone, or placebo alone group. The objectives were to assess the cognitive effect of MAPT interventions (omega 3 supplementation, MI, combined intervention) in non-demented subjects according to amyloid blood status at 12, 36, and 60 months. In this subgroup analysis (n = 483), amyloid status was defined by plasma A[beta]42/40 ratio (cutoff [less than or equal to] 0.0107). The primary outcome measure was the change in cognitive composite score after a 1, 3, and 5-year clinical follow-up. Results The intention-to-treat (ITT) population included 483 subjects (161 positive and 322 negative amyloid participants based on plasma A[beta]42/40 ratio). In the positive amyloid ITT population, we showed a positive effect of MI plus omega 3 on the change in composite cognitive score in 12 (raw p = .0350, 0.01917, 95% CI = [0.0136 to 0.3699]) and 36 months (raw p = .0357, 0.2818, 95% CI = [0.0190 to 0.5446]). After correction of multiple comparisons and adjustments, these differences were not significant (adjusted p = .1144 and .0690). In the per-protocol positive amyloid group (n = 154), we observed a significant difference between the combined intervention and placebo groups at 12 (p = .0313, 0.2424, 0.0571 to 0.4276) and 36 months (p = .0195, 0.3747, 0.1055 to 0.6439) persisting after adjustment. In the ITT and per-protocol analyses, no cognitive effect was observed in the positive and negative amyloid group at 60-month visit. Conclusions These findings suggest a benefit of MI plus omega 3 in positive blood amyloid subjects. This promising trend needs to be confirmed before using blood biomarkers for screening in preventive trials. Trial registration ClinicalTrials.gov Identifier: NCT01513252. Keywords: Clinical trial, Alzheimer's disease, Amyloid blood biomarker, Prevention
Author(s): Julien Delrieu[sup.1] , Bruno Vellas[sup.1] , Sophie Guyonnet[sup.1] , Christelle Cantet[sup.1] , Vitaliy Ovod[sup.2] , Yan Li[sup.2] , James Bollinger[sup.2] , Randall Bateman[sup.2,3] , Sandrine Andrieu[sup.4] , Isabelle Carrié[sup.] [...]
Author(s): Julien Delrieu[sup.1] , Bruno Vellas[sup.1] , Sophie Guyonnet[sup.1] , Christelle Cantet[sup.1] , Vitaliy Ovod[sup.2] , Yan Li[sup.2] , James Bollinger[sup.2] , Randall Bateman[sup.2,3] , Sandrine Andrieu[sup.4] , Isabelle Carrié[sup.] [...]