BARCELONA—A combination of cognitive and physical training plus omega-3 fatty acid supplements may improve cognitive performance significantly among people with subjective memory complaints, according to data presented at the Clinical Trials on Alzheimer’s Disease conference. Among people with more serious memory problems, the combination provides even more benefit by preventing any decline over three years, said Dr. Bruno Vellas, MD, PhD, Chief of the Alzheimer’s Disease Clinical and Research Center at the University Hospital Center in Toulouse, France.
The program was also especially effective in subjects who were homozygous for the high-risk ε4 allele of APOE, said Dr. Vellas.
The findings must be confirmed in larger studies, he said, but they strengthen the growing body of evidence supporting nonpharmacologic tactics for preventing Alzheimer’s disease.
“This [result] confirms the data from FINGER. In FINGER, we had some improvement, but here we are able to show that we can prevent decline, which is maybe even more important, especially for high-risk patients,” Dr. Vellas said.
The Multidomain Alzheimer Preventive Trial
The Multidomain Alzheimer Preventive Trial (MAPT) included 1,680 people who had reported subjective memory complaints to their primary care physicians. It examined the effect of a comprehensive cognitive, nutritional, and physical training program, with or without omega-3 fatty acid supplementation. In addition to the cognitive outcome, MAPT used functional PET imaging to examine brain glucose metabolism at baseline and at six and 12 months, and amyloid plaque burden at 12 to 18 months.
Cognitive training focused on reasoning and memory training. Its main objective was to teach participants how to use adaptive strategies to solve everyday problems—for example, using mnemonics to remember a grocery list.
The physical training component involved at least 150 minutes of moderate exercise each week; walking 30 minutes/day was the most frequently recommended. Participants also received an individually designed at-home exercise plan that was reviewed and updated every six months.
Nutritional counseling was based on the French National Nutrition and Health Program. Eight key guidelines on healthy diet were discussed.
These interventions were all offered in small groups, during 12 two-hour sessions in the first two months. Participants underwent brief individual interviews every six months and intensive booster sessions after one year and two years.
Each supplement capsule contained a specially compounded combination of 400 mg of docosahexaenoic acid (DHA) and 112.5 mg of eicosapentaenoic acid (EPA). It was taken twice per day.
The trial consisted of the following four arms: omega-3 supplements (DHA) alone, placebo capsules alone, training without DHA supplements, and both training and DHA.
Training Program Improved Cognition
The mean age of the study participants was 75. Although the mean Mini-Mental State Examination score was 28, indicating no cognitive impairment, some subjects had mild cognitive impairment. About 40% of participants had a Clinical Dementia Rating (CDR) sum of boxes score of 0.5, indicating very mild Alzheimer’s disease. The rest of the participants had a 0 score. No participant had dementia. About 23% of patients had APOE ε4.
Compliance with the program was very good, Dr. Vellas said. Mean compliance was 71% for the training programs and 84% for the supplements over the three years.
In the intent-to-treat and per-protocol analyses, the training program and the combination of training and DHA were significantly more effective than either DHA or placebo.
Patients taking DHA alone or placebo declined similarly from baseline. Participants in the training program (with or without DHA) had a significant increase in cognitive score during the first year. During the second year, that gain decreased, but cognitive score remained significantly above baseline in both groups.
Dr. Vellas also examined the composite cognitive end point in the subgroup with a 0.5 score on the CDR scale. People taking placebo or DHA only had no improvement and were significantly below baseline by the end of the study. Those who were in the training program only had an increase in scores during the first six months, but the increase rapidly dissipated. By two years, the scores were significantly below baseline, although they were not as low as those in the placebo and DHA-only groups.
The best outcome occurred in the training-program-plus-DHA group. Their test scores remained completely stable during the entire period, suggesting that the combination intervention prevented cognitive decline.
The combination intervention conferred the biggest benefit on participants who were APOE ε4-positive. Their scores rose significantly by 12 months and, although they began to decline, they remained significantly improved through the study’s end. The training program alone also improved the cognitive score by 12 months, but cognitive score returned to baseline by the end of the study. Patients taking placebo or DHA alone had significant declines in cognitive score.