Two studies in the Aug. 25 issue of JAMA have found no significant effects of physical activity and nutrient supplementation on cognitive function.
In one study, Kaycee M. Sink, MD, MAS, of the Wake Forest School of Medicine, Winston-Salem, N.C., and colleagues evaluated whether a 24-month physical activity program would result in better cognitive function, lower risk of mild cognitive impairment or dementia, or both, compared with a health education program.
Epidemiological evidence suggests physical activity is associated with lower rates of cognitive decline. Exercise is associated with improved cerebral blood flow and neuronal connectivity and maintenance or improvement in brain volume. However, evidence from randomized trials has been limited and mixed, according to background information in the JAMA article.
Participants in the Lifestyle Interventions and Independence for Elders study, or LIFE study, (n = 1,635) were assigned randomly to a structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. The study participants were sedentary adults ages 70-89 who were at risk for mobility disability but able to walk about a quarter-mile. Researchers measured cognitive function and incident MCI or dementia at 24 months.
Findings showed the moderate-intensity physical activity intervention did not result in better global or domain-specific cognition compared with the health education program. There also was no significant difference between groups in the incidence of MCI or dementia (13.2% in the physical activity group vs. 12.1% in the health education group), although this outcome had limited statistical power, the researchers found.
“Cognitive function remained stable over 2 years for all participants,” the authors wrote. “We cannot rule out that both interventions were successful at maintaining cognitive function.”
The study did find participants in the physical activity group who were 80 or older and those with poorer baseline physical performance had better changes in executive function composite scores compared with the health education group.
“This finding is important because executive function is the most sensitive cognitive domain to exercise interventions, and preserving it is required for independence in instrumental activities of daily living,” the authors wrote in the JAMA article. “Future physical activity interventions, particularly in vulnerable older adult groups (e.g., ≥80 years of age and those with especially diminished physical functioning levels), may be warranted.”
In another study, Emily Y. Chew, MD, of the National Eye Institute/National Institutes of Health, Bethesda, Md., and colleagues tested the effects of oral supplementation with nutrients on cognitive function.
The prevalence of Alzheimer’s disease, estimated to have affected 5.3 million people in the U.S. in 2015, might triple in the next four decades, according to the Alzheimer’s Association. Epidemiologic studies have suggested diets high in omega-3 long-chain polyunsaturated fatty acids have a protective role in maintaining cognitive function. However, numerous randomized clinical trials failed to show omega-3 LCPUFAs to be effective in treating dementia, according to the study background.
Participants in the Age-Related Eye Disease Study 2, who were at risk for developing late age-related macular degeneration, were assigned randomly to receive LCPUFAs (1 gram) and/or the dietary supplements lutein (10 milligrams)/zeaxanthin (2 milligrams) vs. placebo. All participants also were given varying combinations of vitamins C, E, beta carotene and zinc.
In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every two years during the five-year study. A total of 89% (3,741/4,203) of AREDS2 participants consented to the ancillary cognitive function study, and 93.6% of that group (3,501/3,741) underwent cognitive function testing. The average age of the participants was 72.7 years, and 57.5% were women.
The findings showed no statistically significant differences in change of measures of cognitive function for participants randomized to receive supplements compared with those who were not. The yearly change in the composite cognitive function score was -0.19 for participants randomized to receive LCPUFAs versus -0.18 for those randomized to not receive LCPUFAs, according to the study. Similarly, the yearly change in the composite cognitive function score was -0.18 for participants randomized to receive lutein/zeaxanthin compared with -0.19 for those randomized to not receive lutein/zeaxanthin.
Regarding the lack of effect of the supplements, the authors speculate the supplements were started too late in the aging process and supplementation duration of five years might be insufficient.
“The process of cognitive decline may occur over decades, thus a short-term supplementation given too late in the disease may not be effective,” the authors wrote in the study.
The researchers added observational data regarding dietary intake of specific nutrients such as omega-3 LCPUFAs and antioxidants suggest strong inverse associations with dementia, yet the randomized controlled trials have failed to show beneficial effects. “It is possible that eating foods rather than taking any specific single supplement may have an effect,” the authors wrote.
Editorial cautions against defeatist attitude
In an accompanying editorial, Sudeep S. Gill, MD, MSc, and Dallas P. Seitz, MD, PhD, of Queen’s University, Kingston, Ontario, caution against a defeatist attitude toward lifestyle factors in older adults.
“Although the well-designed RCTs presented by Sink and colleagues and Chew and colleagues failed to demonstrate significant cognitive benefits, these results should not lead to nihilism involving lifestyle factors in older adults,” Gill and Seitz wrote. “It is still likely that lifestyle factors such as diet and physical activity have important roles in the prevention of cognitive decline, dementia and performance of the activities of daily living.
“Physicians should encourage patients of all ages to optimize physical activity levels throughout their life, which may help to reduce the risk of developing dementia and many other adverse health outcomes,” they wrote. “An active lifestyle throughout the lifespan may be more effective in preventing cognitive decline than starting physical activity after the onset of cognitive symptoms. Similarly, adherence to Mediterranean or heart-healthy diets throughout life are likely to be most beneficial in preventing cognitive decline or the onset of dementia in contrast to isolated nutritional supplements initiated late in life.”
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