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
2017
Summary Background No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with
placebofor the prevention of cognitive decline. We tested the effect of omega 3
polyunsaturated fatty acidsupplementation 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 acidsalone, or
placeboalone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to
polyunsaturated fatty acidor
placeboassignment, 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). 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
placebogroup. Between-group differences compared with
placebowere 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
placebogroup, and 0·011 (−0·081 to 0·103; 0·812) for the omega 3
polyunsaturated fatty acidsgroup. 146 (36%) participants in the multidomain plus
polyunsaturated fatty acidsgroup, 142 (34%) in the multidomain plus
placebogroup, 134 (33%) in the
polyunsaturated fatty acidsgroup, and 133 (32%) in the
placebogroup had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus
placebogroup and two in the
placebogroup). 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. Funding French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.
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