title: 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.
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 ClinicalTrials.gov (NCT00672685).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Department of Epidemiology and Public Health, CHU Toulouse, Toulouse, France. Electronic address: sandrine.andrieu@univ-tlse3.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Andrieu
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Guyonnet
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Department of Epidemiology and Public Health, CHU Toulouse, Toulouse, France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Coley
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Cantet
authors.affiliation: Geriatrics Department, Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonnefoy
authors.affiliation: Geriatrics Department, Hospital of Tarbes, Tarbes, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Bordes
authors.affiliation: Geriatrics Department, Hospital of Foix, Foix, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Bories
authors.affiliation: Geriatrics Department, Hospital of Castres, Castres, France.
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Cufi
authors.affiliation: Geriatrics Department, Memory Research Resource Center, University Hospital of Limoges, Limoges, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Dantoine
authors.affiliation: INSERM U897, Memory Research Resource Center for Alzheimer's Disease, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.affiliation: Geriatrics Department, Hospital of Lavaur, Lavaur, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Desclaux
authors.affiliation: Memory Research Resource Center for Alzheimer's Disease, Department of Neurology, University Hospital of Montpellier, Montpellier, France; INSERM U1183, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gabelle
authors.affiliation: Geriatrics Department, Hospital of Tarbes, Tarbes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Gasnier
authors.affiliation: Geriatrics Department, Hospital of Princess Grace, Monaco.
authors.forename: Alain
authors.initials: A
authors.lastname: Pesce
authors.affiliation: Geriatrics Department, Hospital of Montauban, Montauban, France.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sudres
authors.affiliation: Memory Research Resource Center for Alzheimer's Disease, Department of Neurology, University Hospital of Montpellier, Montpellier, France; INSERM U1061, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Touchon
authors.affiliation: Memory Center CHU, CoBTeK 7276, University Côte d'Azur, Nice, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.affiliation: Memory Research Resource Center, Neurology Department, University Hospital of Dijon, Dijon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rouaud
authors.affiliation: Nutrition Department, Agrocampus-INRA, Rennes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Legrand
authors.affiliation: Department of Nuclear Medicine, CHU Toulouse, Purpan University Hospital, Toulouse, France; Toulouse NeuroImaging Centre, University of Toulouse, INSERM, UPS, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.affiliation: Pierre Fabre Research Institute, Toulouse, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Caubere
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carrié
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Ousset
authors.affiliation: INSERM UMR 1027, Toulouse, France; University of Toulouse III, Toulouse, France; Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000187:drug effects; D015928:Cognitive Behavioral Therapy; D019587:Dietary Supplements; D004311:Double-Blind Method; D005081:Exercise Therapy; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000517:prevention & control*; D009483:Neuropsychological Tests; D016896:Treatment Outcome
chemical_list: D015525:Fatty Acids, Omega-3