Multi-domain intervention plus omega-3 supplementation improves cognition in older people with memory complaint

Results to be announced at the 8th International Conference on Clinical Trials for Alzheimer's Disease (CTAD) suggest that combining a multidomain program of nutritional counseling, exercise, and cognitive and social stimulation with omega-3 fatty acid supplementation may help slow cognitive decline in older adults, especially those who have mild cognitive impairment (MCI).

The Multidomain Alzheimer's Preventive Trial (MAPT) enrolled a group of nearly 1700 older adults with memory complaints, slow walking speed, and limitation of at least one instrumental activity of daily living (IADL). The participants were randomized to one of four groups for the three-year intervention study: placebo, omega-3 supplementation (800 mg DHA per day), placebo plus multidomain intervention, and omega-3 plus multidomain intervention. DHA is an omega-3 fatty acid that is thought to have anti-inflammatory effects and has been linked to a lower risk of Alzheimer's disease.

Testing at the beginning of the study showed that the groups were balanced in terms of age, education level, cognitive scores, and presence of the genetic marker, ApoE4, which increases the risk of developing Alzheimer's disease. About 40% of the participants in each group were identified as having MCI.

Six months after starting the program, and then again at 12, 24, and 36 months, the participants were tested using a composite cognitive battery that evaluated cognitive domains that are affected in people with Alzheimer's disease dementia - episodic memory, orientation, executive function, and verbal fluency. Pre-specified statistical analyses assessed the effect of several baseline variables on outcome, including cognitive scores, blood levels of DHA, and the presence of the ApoE4.

According to Professor Bruno Vellas, M.D., geriatrician and chair, Gérontopôle and the University of Toulouse, who led the study, the data show a clear, long- term effect in the multidomain group. "Moreover, the results are very significant in the pre-specified subgroup with MCI, probably because they have more decline."

A secondary analysis showed that participants with low baseline DHA also showed significant benefits from the multidomain intervention plus DHA supplementation. "It may be that we first need to restore brain health with DHA to be able to see the effect of the multi-domain intervention," said Vellas.

Ancillary imaging studies confirm the clinical outcome, said Professor Vellas, showing that the patients receiving the multi-domain intervention plus DHA have statistically significant improvement in brain metabolism, as shown in fluorodeoxyglucose positron emission tomography (FDG PET) scans, compared to controls. The results are even more pronounced in people with the genetic marker ApoE4, which increases the risk of developing Alzheimer's disease, and in those with evidence of amyloid deposition in the brain.

Participants in this study will be followed for an additional two years to show whether the benefit of the intervention is maintained over time. Professor Vellas said the research team plans to develop kits to easily measure red blood cell levels of DHA to identify people who should receive supplements. They also plan a follow up study targeting only those individuals who are identified as being at high risk of progression. Finally, he said they are working on smart phone apps that will enable people to use the multi-domain program at home for a more sustained effect.

Other investigators in the study include T. Voisin, C. Dufouil, I. Carrie, S. Gillette- Guyonnet, S. Andrieu, W.W. Ousset, F. Lala, C. Faisant, J. Delrieu, B. Fougere, C. Dupuy, and C. Cantet from Gérontopôle and the University of Toulouse; N. Coley from the University of Toulouse; A. Gabelle and J. Touchon from the University Hospital, Montpellier; T. Dantoine from the University Hospital, Limoge; J-F Dartiques from the University Hospital, Bordeaux; M-N Cuffi from the Hospital of Castres; S. Bordes and Y. Gasnier from the Hospital of Tarbes; P. Robert from the University Hospital, Nice; L. Bories from the Hospital of Foix; O. Rouaud from University Hospital of Dijon; F. Desclaux from the Hospital of Lavaur; K. Sudres from the Hospital of Montauban; M. Bonnefoy from the Centre Hospitalier Lyon- Sud; A. Pesce from the Hospital of Princess Grace, Monaco; S. Belleville from the Institut Universitaire de Gériatrie de Montréal, Canada; S. Willis from the University of Washington, USA; and M. Weiner, from the University of California, San Francisco, USA.