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.

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). 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. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Chronic physical activity preserves efficiency of proprioception in postural control in older women.

The purpose of this study was to compare the effects of proprioceptive disruption on postural control for participants of different ages according to their physical and/or sport activity levels. Two groups of young and old participants who practiced chronic physical and/or sport activities (young active [n = 17; average age 20.5 +/- 1.1 yr] and old active [n = 17; average age 74.0 +/- 3.8 yr]) and two groups of young and old participants who did not practice physical and/or sport activities (young sedentary [n = 17; average age 20.0 +/- 1.3 yr] and old sedentary [n = 17; average age 74.7 +/- 6.3 yr]) participated in the study. They were compared in a bipedal quiet stance reference condition and a bilateral Achilles tendon vibration condition. Center of foot pressure displacements and frequency analysis were compared between the groups. The results indicated that when proprioceptive information was disrupted, the postural control disturbance was more important for the old sedentary group than for the other groups. There were no differences between the old active group and the young sedentary group. Postural control was less altered for the young active group than for the other groups. Aging decreases the efficiency of postural control regardless of the assessment conditions. Physical and sport activities may compensate for the disturbing effects of proprioceptive perturbation through a better use of sensory information whatever the age of the participants.

Discrepancy in the involution of the different neural loops with age.

The purpose of the study was to compare the effects of sensory manipulations on postural control for subjects of different ages. A young group of subjects (n = 17; 20.0 ± 1.3 years) and an old group of subjects (n = 17; 74.7 ± 6.3 years) were compared in 14 postural conditions [2 reference conditions and 12 sensory manipulation conditions: eyes closed, cervical collar, tendon vibration, electromyostimulation, galvanic vestibular stimulation (2 designs), foam surface] on a force platform. Spatio-temporal parameters of the center of foot pressure displacement were analyzed. When vestibular or proprioceptive afferences were manipulated, the old group was more disturbed than the young group. In addition, when myo-articular proprioceptive afferences were the only non-manipulated information source, the old group was also more disturbed than the young group. Hence, the inability to correctly interpret proprioceptive information and/or the impairment of myo-articular information would appear to be the major factor causing postural control deterioration. Moreover, concerning the vestibular system, it may be that aging alters the central integration of vestibular afferences. These results suggest that aging differently affects the functional ability of the different neural loops in postural control.