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Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial

Sandrine Andrieu 1, 2, 3 Sophie Guyonnet 2, 1, 3 Nicola Coley 1, 2, 3 Christelle Cantet 1, 2, 3 Marc Bonnefoy 4, 5 Serge Bordes 6 Lawrence Bories 7 Marie Cufi 8 Thierry Dantoine 9 François Dartigues 10 François Desclaux 11 Audrey Gabelle 12, 13 Yannick Gasnier 6 Alain Pesce 14 Kristel Sudres 15 Jacques Touchon 12, 16 Philippe Robert 17 Olivier Rouaud 18 Philippe Legrand 19 Pierre Payoux 20 Jean-Paul Caubere 21 Michael Weiner 22 Isabelle Carrie 3 Pierre Ousset 3, 1, 2 Bruno Vellas 3, 1, 2 Brigitte Brigitte Catherine Faisant François Lala Julien Delrieu 23 Hélène Villars Emeline Combrouze Carole Badufle Audrey Zueras Christophe Morin 24 Gabor Abellan van Kan Charlotte Dupuy 25 Yves Rolland 26 Celine Caillaud Bertrand Fougère 27 Sherry Willis Sylvie Belleville Brigitte Gilbert 28 Francine Fontaine Marc Marcet Fleur Delva 29 Alexandra Foubert Sandrine Cerda Marie Noëlle-Cuffi Corinne Costes Patrick Manckoundia 30 Valérie Quipourt 30 Sophie Marilier 30 Evelyne Franon 31 Marie Pader Marie Basset Bruno Lapoujade Valérie Faure Michael Li Yung Tong Christine Malick-Loiseau Evelyne Cazaban-Campistron Colette Blatge Cécile Laubarie-Mouret Isabelle Saulnier 32 Pierre Clément 33 Marie Picat Laurence Bernard-Bourzeix 34 Stéphanie Willebois Iléana Desormais 35 Noëlle Cardinaud 32 Pierre Livet 36 Pascale Rebaudet Claire Gédéon Catherine Burdet Flavien Terracol Stéphanie Roth 37 Sylvie Chaillou Sandrine Louchart Nicolas Lebrun 38 Nadège Barro-Belaygues Karim Bennys 12 Aurélia Romano Lynda Touati Cecilia Marelli 39 Cecile Pays 40 Franck Le Duff 41 Claire Gervais 42 Sébastien Gonfrier Danièle Begorre Christian Carpuat Khaled Khales François Lefebvre 43 Samira Misbah El Idrissi Pierre Skolil Pierre Salles 44 Carole Dufouil 45 Stéphane Lehéricy 46 Marie Chupin 46 François Mangin Ali Bouhayia Michèle Allard 47 Fréderic Ricolfi 48 Dominique Dubois Marie Paule Bonceour Martel François Cotton Alain Bonafé 49 Stéphane Chanalet 50 François Hugon Fabrice Bonneville 3 Christophe Cognard 51 François Chollet 3 Thierry Voisin 52 Sophie Peiffer Anne Hitzel 53 Michel Zanca 54 Jacques Monteil Jacques Darcourt 55 Laurent Molinier 56 Helene Derumeaux 56 Nadège Costa Christian Vincent Bertrand Perret 57 Claire Vinel 58 Pascale Olivier-Abbal
Abstract : BACKGROUND:No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.METHODS:The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with (NCT00672685).FINDINGS:1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events.INTERPRETATION:The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings.
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Submitted on : Monday, July 2, 2018 - 11:08:06 AM
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Sandrine Andrieu, Sophie Guyonnet, Nicola Coley, Christelle Cantet, Marc Bonnefoy, et al.. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. The Lancet Neurology, Elsevier, 2017, 16 (5), pp.377 - 389. ⟨10.1016/S1474-4422(17)30040-6⟩. ⟨hal-01827359⟩



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