B Vellas1, I Carrie2, S Gillette-Guyonnet1, J Touchon3, T Dantoine4, J F Dartigues5, M N Cuffi6, S Bordes7, Y Gasnier7, P Robert8, L Bories9, O Rouaud10, F Desclaux11, K Sudres12, M Bonnefoy13, A Pesce14, C Dufouil15, S Lehericy16, M Chupin16, J F Mangin17, P Payoux18, D Adel19, P Legrand20, D Catheline20, C Kanony21, M Zaim21, L Molinier22, N Costa22, J Delrieu2, T Voisin1, C Faisant2, F Lala2, F Nourhashémi1, Y Rolland1, G Abellan Van Kan1, C Dupuy23, C Cantet1, P Cestac1, S Belleville24, S Willis25, M Cesari1, M W Weiner26, M E Soto1, P J Ousset1, S Andrieu27. 1. Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France ; INSERM UMR 1027, Toulouse, France ; University of Toulouse III, Toulouse, France. 2. Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France. 3. Department of Neurology, Memory Research Resource Center for Alzheimer's Disease, University Hospital of Montpellier, Montpellier, France. 4. Geriatrics Department, Memory Research Resource Center, University Hospital of Limoges, Limoges, France. 5. INSERM U897, Memory Research Resource Center for Alzheimer's Disease, University Hospital of Bordeaux, Bordeaux, France. 6. Geriatrics Department, Hospital of Castres, Castres, France. 7. Geriatrics Department, Hospital of Tarbes, Tarbes, France. 8. Memory Research Resource Center, University Hospital of Nice, Nice, France. 9. Geriatrics Department, Hospital of Foix, Foix, France. 10. Memory Research Resource Center, Neurology Department, University Hospital of Dijon, Dijon, France. 11. Geriatrics Department, Hospital of Lavaur, Lavaur, France. 12. Geriatrics Department, Hospital of Montauban, Montauban, France. 13. Geriatrics Department, Centre Hospitalier Lyon-Sud, Lyon, France. 14. Geriatrics Department, Hospital of Princess Grace, Monaco. 15. INSERM Center U897, CIC-EC7, Bordeaux University, Department of Public Health of CHU Bordeaux, Bordeaux, France. 16. Neuroradiology Department, Pitié-Salpêtrière Hospital, Paris, France. 17. CATI, NeuroSpin, CEA-Saclay Center, Gif-sur-Yvette, France. 18. INSERM UMR 825, Toulouse, France ; Department of Nuclear Medicine, CHU Toulouse, Purpan University Hospital, Toulouse, France. 19. INSERM UMR 825, Toulouse, France. 20. Nutrition Department, Agrocampus-INRA, Rennes, France. 21. Institut de Recherche Pierre Fabre, Toulouse, France. 22. INSERM UMR 1027, Toulouse, France ; University of Toulouse III, Toulouse, France ; Department of Medical Information, CHU Toulouse, Toulouse, France. 23. Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France ; INSERM UMR 1027, Toulouse, France. 24. Research Center, Institut Universitaire de Gériatrie de Montréal, Montréal, Canada. 25. Department of Psychiatry and Behavioral Sciences, University of Washington, Washington, USA. 26. University of California, San Francisco, California, United States. 27. Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France ; INSERM UMR 1027, Toulouse, France ; University of Toulouse III, Toulouse, France ; Department of Epidemiology and Public Health, CHU Toulouse, Toulouse, France.
Abstract
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.
RCT Entities:
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.
Authors: L P Fried; C M Tangen; J Walston; A B Newman; C Hirsch; J Gottdiener; T Seeman; R Tracy; W J Kop; G Burke; M A McBurnie Journal: J Gerontol A Biol Sci Med Sci Date: 2001-03 Impact factor: 6.053
Authors: Abhinay D Joshi; Michael J Pontecorvo; Chrisopher M Clark; Alan P Carpenter; Danna L Jennings; Carl H Sadowsky; Lee P Adler; Karel D Kovnat; John P Seibyl; Anupa Arora; Krishnendu Saha; Jason D Burns; Mark J Lowrey; Mark A Mintun; Daniel M Skovronsky Journal: J Nucl Med Date: 2012-02-13 Impact factor: 10.057
Authors: I Carrié; G Abellan van Kan; S Gillette-Guyonnet; S Andrieu; J-F Dartigues; J Touchon; T Dantoine; O Rouaud; M Bonnefoy; P Robert; M-N Cuffi; L Bories; S Bordes; Y Gasnier; F Desclaux; K Sudres; A Pesce; B Vellas Journal: J Nutr Health Aging Date: 2012-04 Impact factor: 4.075
Authors: Frank Jessen; Steffen Wolfsgruber; Birgitt Wiese; Horst Bickel; Edelgard Mösch; Hanna Kaduszkiewicz; Michael Pentzek; Steffi G Riedel-Heller; Tobias Luck; Angela Fuchs; Siegfried Weyerer; Jochen Werle; Hendrik van den Bussche; Martin Scherer; Wolfgang Maier; Michael Wagner Journal: Alzheimers Dement Date: 2013-01-30 Impact factor: 21.566
Authors: Sandrine Andrieu; Nicola Coley; Paul Aisen; Maria C Carrillo; Steven DeKosky; Jane Durga; Howard Fillit; Giovanni B Frisoni; Lutz Froelich; Serge Gauthier; Roy Jones; Linus Jönsson; Zaven Khachaturian; John C Morris; Jean-Marc Orgogozo; Pierre-Jean Ousset; Philippe Robert; Eric Salmon; Cristina Sampaio; Frans Verhey; Gordon Wilcock; Bruno Vellas Journal: J Alzheimers Dis Date: 2009 Impact factor: 4.472
Authors: P Payoux; J Delrieu; A Gallini; D Adel; A S Salabert; A Hitzel; C Cantet; M Tafani; D De Verbizier; J Darcourt; Ph Fernandez; J Monteil; I Carrié; T Voisin; S Gillette-Guyonnet; M Pontecorvo; B Vellas; S Andrieu Journal: Eur J Nucl Med Mol Imaging Date: 2015-05-08 Impact factor: 9.236
Authors: S Y Moon; P de Souto Barreto; M Chupin; J F Mangin; A Bouyahia; L Fillon; S Andrieu; B Vellas Journal: J Nutr Health Aging Date: 2018 Impact factor: 4.075
Authors: C Hooper; P De Souto Barreto; P Payoux; A S Salabert; S Guyonnet; S Andrieu; S Sourdet; J Delrieu; B Vellas Journal: J Nutr Health Aging Date: 2017 Impact factor: 4.075
Authors: M Tabue-Teguo; P Barreto de Souza; C Cantet; S Andrieu; N Simo; B Fougère; J F Dartigues; B Vellas Journal: J Nutr Health Aging Date: 2018 Impact factor: 4.075