BARCELONA – A combination of cognitive and physical training plus omega-3 fatty acid supplements boosted cognitive performance significantly in a group of people with subjective memory complaints.
Among those with more serious memory issues, the combination worked even better, preventing any decline at all over the 3-year study period, Dr. Bruno Vellas said at the Clinical Trials on Alzheimer’s Disease conference.
The program was also especially effective in subjects who were homozygous for the high-risk e4 allele of the apolipoprotein E gene, said Dr. Vellas, chief of the Alzheimer’s Disease Clinical and Research Center at the University Hospital Center in Toulouse, France.
The findings must be confirmed in larger studies, he said, but they strengthen the growing body of evidence supporting nonpharmacologic Alzheimer’s prevention tactics.
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“This 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 (MAPT) comprised 1,680 people who had reported subjective memory complaints to their primary care physician. It examined the effect of a comprehensive cognitive, nutrition, 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 6 and 12 months, and amyloid plaque burden at 12-18 months.
Cognitive training focused on reasoning and memory training. Its main objective was to teach participants how to use adaptive strategies in solving 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 6 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 2-hour sessions in the first 2 months. There were brief individual interviews every 6 months, and intensive booster sessions after 1 year and 2 years.
Each supplement capsule contained a specially compounded combination of 400 mg docosahexaenoic acid (DHA) and 112.5 mg eicosapentaenoic acid (EPA). It was taken twice a day.
The trial consisted of four arms: omega-3 supplements (DHA) alone; placebo capsules alone; training without DHA supplements; and both training and DHA
The mean age of the study participants was 75 years. While the mean Mini Mental State Exam score was 28, indicating no cognitive impairment, some subjects did dip down into the mild cognitive impairment range. About 40% had a Clinical Dementia Rating sum of boxes (CDR) score of 0.5 (very mild Alzheimer’s); the rest had a 0 score. No one had frank dementia. About 23% were positive for APOE e4.
Compliance with the program was very good, Dr. Vellas said: a mean of 71% for the training programs and 84% for the supplements over the 3 years.
In both 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.
Those taking DHA alone or placebo declined similarly from baseline. Those in the training program (with or without DHA) experienced a significant uptick in cognitive score during the first year. During the second year that gain fell, but it still remained significantly above baseline in both groups.
Dr. Vellas also examined the composite cognitive endpoint in the subgroup with a 0.5 score on the CDR scale. Those taking placebo or DHA-only experienced no improvement and fell significantly below baseline by the end of the study. Those who were in the training program only experienced a boost in scores in the first 6 months, which rapidly fell off. By 2 years, the scores were significantly below baseline, although not as depressed 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 over the entire period, suggesting that the combination intervention prevented cognitive decline.
It conferred the biggest benefit on those who were APOE e4-positive. Their scores rose significantly by 12 months and, although they did begin to decline, they remained significantly improved through the study’s end. The training program alone also improved the cognitive score by 12 months, but that dipped back to baseline by the end of the study. Those taking placebo or DHA alone experienced significant score declines.