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,Marie-Noëlle-Cuffi ,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,
Abstract
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 Aβ42/40 ratio (cutoff ≤ 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 Aβ42/40 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.
Publisher
Springer Science and Business Media LLC
Subject
Cognitive Neuroscience,Neurology (clinical),Neurology