MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

Vitamin D supplementation in older adults: searching for specific guidelines in nursing homes.

BACKGROUND: The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. DESIGN: Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. RESULT: Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. CONCLUSION: A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

Recruitment strategies for preventive trials. The MAPT study (MultiDomain Alzheimer Preventive Trial).

1680 participants were randomized over the recruitment period in MAPT study. A total of 1290 participants were recruited in the 7 University Hospital centers, and 390 participants in the 6 memory clinics around Toulouse Gerontopole / Alzheimer Disease research clinical center. The first randomization was on May 30, 2008, and the targeted number of randomized participants was reached on February 24, 2011; 2595 subjects were finally screened, of which 1680 fulfilled the eligibility criteria which represents 64.8%. Approximately, one quarter of screened people refused to participate after the detailed presentation of the study and 4.3% were still interested in participating but missed for unknown reasons the baseline visit even after repeated contacts. Of the 1810 subjects who signed the consent for participating to the study at the baseline visit, 130 (7.1%) were excluded because one of the eligibility criteria was not satisfied. Interestingly, the higher percentage of randomizations compared to screened participants is the personal contact source; almost 85 % of screened participants entered in the study. In an equivalent way, Medias and conferences are efficient recruiting sources to enrol volunteers in the study. Unexpectedly, only about 60% of screened participants from the hospital and GP sources were randomized and 33.2% from health care services. Almost a quarter of the randomized participants come from the hospital outpatients clinics and approximately 20% from public conferences. A total of 1128 contacts yielded to 556 screened volunteers and 345 randomized participants in the coordinating center of Toulouse. Thus, 30 % of contacts were recruited.

Effects of branched amino acids supplementation in malnourished elderly with catabolic status.

BACKGROUND: Among various nutrients branched amino acids (BCAAS) have been shown to be the most responsible for the stimulation of protein synthesis in various situations including catabolic states. OBJECTIVES: We evaluated the effect of a small amount of proteins enriched with BCAAs (0.4 g/kg/day and 0.2 g/kg/day BCAAs) on body weight and composition; nitrogen balance, energy intake and inflammation after 2 weeks of supplementation in acute elderly with catabolic status. DESIGN: Two weeks randomized controlled trial. SETTING: Geriatric department of teaching hospital. SUBJECTS: Thirty patients with malnutrition and inflammatory process (MNA < 24, albumin < 30 g/l and CRP > or = 20 mg/l) who agreed to participate in the study were consecutively included. METHODS: Body composition was determined by labelled water dilution method; resting energy expenditure (REE) was determined by indirect calorimetry; energy intake was calculated for a 3 days period at D1 and D12. Nutritional and inflammatory proteins and cytokines (IL-6 and TNF) were measured at day 1 and 14. RESULTS: No difference was observed at day 14 between supplemented (S) and control (C) group for weight (S: 58.0 +/- 11.8 kg and C: 60.0 +/- 15.9 kg); fat free mass (S: 40.7 +/- 8.3 kg and C: 40 +/- 8.2 kg); nitrogen balance (S: 1.34 +/- 2.21 g/day and C: 0.59 +/- 4.47 g/day); and energy intake (S: 20 +/- 3.6 kcal/day and C: 20.5 +/- 8.6 kcal/day). Energy intake was at similar level than REE and clearly less than energy requirement in C and S. A significant decrease was observed for orosomucoid and Prognostic Inflammatory and Nutritional Index (PINI) in S. CONCLUSION: Our results do not confirm improvement of nutritional status with enriched BCAAs supplementation as suggested in the literature. Persistence of inflammatory condition may be an explanation despite an improvement of inflammatory status was observed in the supplemented group. Those results show clearly that energy requirements are not covered in acute hospitalized elderly people. The fact that not only energy intake but also REE are decreased brings a new insight on catabolic situations.

IANA task force on nutrition and cognitive decline with aging.

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

The effects of exercise and protein-energy supplements on body composition and muscle function in frail elderly individuals: a long-term controlled randomised study.

Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly. To our knowledge, the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn. We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly, and would bring about concomitant benefits in body composition and muscle power. Accordingly, this exercise and nutritional combination was assessed in the frail elderly in a 9-month randomised trial with a factorial design. Fifty-seven elderly volunteers over 72 years, from sixteen retirement homes in Lyon, France participated in the study. Dietary supplements were compared with placebo, and physical exercise was compared with memory training. Main outcome measures were fat-free mass (FFM) and muscle power. FFM was determined by labelled water, and muscle power was measured by a leg-extensor machine. At 9 months, the compliance was 63 % for exercise sessions, and 54 % for nutritional supplements. In patients with dietary supplements, muscle power increased by 57 % at 3 months (P=0.03), and showed only a tendency at 9 months; although FFM increased by 2.7 % at 9 months, the difference was not significant (P=0.10). Exercise did not improve muscle power at 9 months, but improved functional tests (five-time-chair rise, P=0.01). BMI increased with supplements (+3.65 %), but decreased with placebo (-0.5 %) at 9 months (P=0.007). A long-term combined intervention is feasible in frail elderly individuals with a good rate of compliance. Nutritional supplements and exercise may improve muscle function. Despite no significant results on FFM, due to the limited number of volunteers, combined intervention should be suggested to counteract muscle weakness in the frail elderly.