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
Volume 16, No. 5, p377–389, May 2017

Prof Sandrine Andrieu, Sophie Guyonnet, PhD, Nicola Coley, PhD, Christelle Cantet, MSc, Prof Marc Bonnefoy, MD, Serge Bordes, MD, Lawrence Bories, MD, Marie-Noëlle Cufi, MD, Prof Thierry Dantoine, MD, Prof Jean-François Dartigues, MD, Françoise Desclaux, MD, Prof Audrey Gabelle, MD, Yannick Gasnier, MD, Alain Pesce, MD, Kristel Sudres, MD, Prof Jacques Touchon, MD, Prof Philippe Robert, MD, Olivier Rouaud, MD, Prof Philippe Legrand, PhD, Prof Pierre Payoux, MD, Jean-Paul Caubere, PharmD, Prof Michael Weiner, MD, Isabelle Carrié, PhD, Pierre-Jean Ousset, MD, Prof Bruno Vellas, MD



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.


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 ClinicalTrials.gov (NCT00672685).


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