Supplements, Exercise Fail to Improve Cognitive Function

Fran Lowry

September 03, 2015

A physical activity program and nutrient supplementation interventions failed to improve cognitive function and lower the risk for mild cognitive impairment (MCI) or dementia, according to two new studies.

In one trial, led by Kaycee M. Sink, MD, from Wake Forest School of Medicine, Winston-Salem, North Carolina, a 24-month, moderate-intensity physical activity program failed to boost cognition in sedentary seniors when compared with a health education program.

In a separate report, researchers led by Emily Y. Chew, MD, from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, found oral supplements of omega-3 fatty acids, lutein and zeaxanthin, also failed to improve cognitive function among older individuals at risk for late age-related macular degeneration.

Dr Kaycee M. Sink

However, the negative results from these trials are not necessarily disappointing, Sudeep Gill, MD, from Queen's University, Kingston, Ontario, Canada, told Medscape Medical News. He and his colleague Dallas P. Seitz, MD, PhD, also from Queen's University, authored a corresponding editorial on the two studies.

"These results have to be interpreted in the context of what the comparison groups were doing, the potential methodological limitations of the trials, such as only a few years of follow-up, and the totality of the evidence from previous studies. No single study should be interpreted as the only results that matter. Results always have to be taken in the context of previous work. In this case, I think there are a lot of good reasons to continue to encourage older adults to stay active physically and socially," Dr Gill said.

Dr Sink agrees. "While physical activity wasn't proven to be better than attending health education seminars in our study, both interventions were likely helping older adults maintain their cognitive function," she told Medscape Medical News.

The two studies and accompanying editorial are published in the August 25 issue of JAMA.

LIFE Study

In their randomized trial, dubbed the Lifestyle Interventions and Independence for Elders (LIFE) study, Dr Sink and her team enrolled 1635 community-dwelling participants at eight centers in the United States from February 2010 until December 2011.

The participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 meters within 15 minutes at study entry.

Half (n = 818) of the participants were randomly assigned to the physical activity program, which consisted of walking, resistance training, flexibility, and balance exercises done at their local center two times a week and at home three to four times per week.

The remaining 817 participants were randomly assigned to health education once a week for the first 26 weeks, and at least once a month thereafter, as well as upper-extremity stretching and flexibility exercises.

In the workshops, which lasted 60 to 90 minutes, participants learned about travel safety, age-appropriate preventive services, legal and financial issues, and nutrition.

None of the study participants had a diagnosis of dementia or significant cognitive impairment on the Modified Mini-Mental State Examination.

Cognitive function and incident MCI or dementia were assessed at 24 months by using the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range, 0 to 133, where higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task).

The researchers found that the physical activity intervention did not result in better global or domain-specific cognition compared with the health education program.

The mean DSC task scores were 46.26 points for the physical activity group compared with 46.28 for the health education group (mean difference, –0.01 points; 95% confidence interval [CI], –0.80 to 0.77 points; P = .97).

The mean HVLT-R delayed recall scores were 7.22 for the physical activity group compared with 7.25 for the health education group (mean difference, –0.03 words; 95% CI, –0.29 to 0.24 words; P = .84).

However, the physical activity intervention was more beneficial for older (>80 years) and less fit participants. These individuals showed better changes in executive function than did those who received the health education intervention (P = .01 for both).

"We expected to see that those who were in the physical activity group would be doing better in regards to memory and thinking after 2 years than those who were attending the education seminars, but instead we found that both groups were doing the same, one was not better than the other," Dr Sink noted.

"But interestingly, both groups had generally maintained their cognitive function over the course of the 2 years, suggesting that both the physical activity and attendance at education seminars were helpful in preserving cognition," she said.

"Because exercise is good for many aspects of health, even if we didn't prove it was better for the brain than a cognitively and socially stimulating activity, I would still recommend that older adults get 150 minutes of exercise a week," Dr Sink said.


In the second study, Dr Chew and colleagues tested the effects of oral supplementation with nutrients on cognitive function.

"Epidemiologic studies have suggested that diets high in omega-3 long-chain polyunsaturated fatty acids have a protective effect in maintaining cognitive function, but numerous randomized trials have failed to show that the omega-3 fatty acids are effective in treating dementia," Dr Chew told Medscape Medical News.

In the study, dubbed the Age-Related Eye Disease Study 2 (AREDS2), retinal specialists in 82 US academic and community medical centers enrolled and observed 4203 participants who were at risk for late age-related macular degeneration from October 2006 to December 2012.

In addition to eye examinations, 3501 participants received cognitive function testing by telephone by trained personnel at baseline and every 2 years during the 5-year study.

The mean age of the participants was 72.7 years (standard deviation [SD], 7.7 years), and 57.5% were women.

The participants were randomly assigned in a 1:1:1:1 allocation to take one of the following study supplements daily:

  1. Placebo;

  2. Docosahexaenoic acid (DHA), 350 mg, and eicosapentaenoic acid (EPA), 650 mg;

  3. Lutein/zeaxanthin; or

  4. DHA/EPA and lutein/zeaxanthin

Change of measures of cognitive function did not significantly differ between participants who were randomly assigned to receive supplements and those who were not.

The yearly change in the composite cognitive function score was –0.19 for participants randomly assigned to receive long-chain polyunsaturated fatty acids (LCPUFAs) vs –0.18 for those assigned to no LCPUFAs.

A similar result was seen for patients randomly assigned to receive the other nutritional supplements.

The yearly change in the composite cognitive function score was –0.18 for participants assigned to receive lutein/zeaxanthin vs –0.19 for those assigned to not receive lutein/zeaxanthin.

"These supplements may have been started too late in the aging process, when participants were too old," Dr Chew commented.

Still, she said, "We can't depend on supplements. They are not going to do it. The fact that we are studying patients at a much older age tells us we can't turn the clock back. This has to be done much earlier. It may be a wise thing to start eating well from the get-go.

"As a nation, we want a quick fix with pills, but we need to have a lifetime of good nutritional intake, and living a healthy lifestyle," Dr Chew added.

"AREDS2 found no cognitive benefit of one type of dietary supplement, long-chain polyunsaturated fatty acids, as compared to another type, lutein/zeaxanthin. These results aren't very surprising, as most studies of specific dietary supplements have not shown they have any significant cognitive benefits," Dr Gill said.

"Instead, other research has emphasized the potential benefits of an overall change in the dietary profile, rather than a specific diet supplement in a pill. A recent trial, the PREDIMED trial, suggested that a Mediterranean diet supplemented with olive oil or nuts might help protect cognitive function. Previous results from PREDIMED and other studies suggested Mediterranean diets have benefits for cardiovascular outcomes as well," he said.

Dr Gill added that the LIFE study "adds important information but doesn't stand alone."

"I would continue to encourage older adults to stay physically and mentally active and to maintain a strong social network," he said. "A well-balanced and heart-healthy diet such as the Mediterranean diet might help preserve cognitive function."

A recent related study called the FINGER trial was published in The Lancet and suggested that combining exercise and diet along with monitoring of vascular risk factors might have cognitive benefits, Dr Gill added. "More work is needed to help find the right combination of strategies to help prevent cognitive decline and dementia in older adults," he said.

The LIFE study was sponsored by the National Institutes of Health; the National Institute on Aging; and the National Heart, Lung, and Blood Institute (NHLBI). AREDS2 was sponsored by the National Eye Institute, the National Institutes of Health, the Department of Health and Human Services, the Office of Dietary Supplements, the National Center for Complementary and Integrative Health, the National Institute on Aging, the NHLBI, and the National Institute of Neurological Disorders and Stroke. Dr. Sink, Dr. Chew, Dr. Gill, and Dr. Seitz have disclosed no relevant financial relationships.

JAMA 2015;314:791-801, 781-790, 774-775. Sink et al Abstract Chew et al Abstract Editorial


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