I wish physical activity and nutrient supplementation would improve cognitive function in older people, but that might not be the case

Two new studies out in JAMA today. First up, “Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial“:

IMPORTANCE Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed.

OBJECTIVE To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program.

DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m.

INTERVENTIONS 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.

MAIN OUTCOMES AND MEASURES Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months.

We have lots of epidemiologic evidence that physical activity is associated with better cognition. But that could be reverse correlation. We need an RCT. This is it.

Researchers randomized more than 1600 elderly people who were sedentary to (1) a structured, moderate intensity physical activity program, including walking, resistance training, and flexibility exercises, or (2) a control health education program of workshops and upper-extremity stretching.

They measured a number of cognitive outcomes, including the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale and the revised Hopkins Verbal Learning Test. They also measured global and executive cognitive function and dementia two years after the intervention.

At 2 years, the scored of the cognititve tests were no different between the groups. On a 133 point scale, the mean scores of the DSC were 46.26 in the physical activity group and 46.28 in the control group. The HVLT (which could score up to 12) was 7.22 in the physical activity group and 7.25 in the control group.

There were also no significant differences in the measures of global or executive cognitive function, nor any in the diagnosis of cognitive impairment or dementia.

The second study tried a different approach. “Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial“:

IMPORTANCE Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease.

OBJECTIVE To test the effects of oral supplementation with nutrients on cognitive function.

DESIGN,SETTING, AND PARTICIPANTS In a double-masked randomized clinical trial
(the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study.

INTERVENTIONS Long-chain polyunsaturated fatty acids (LCPUFAs)(1g)and/or lutein
(10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc.

MAIN OUTCOMES AND MEASURES The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from −22 to 17, with higher scores representing better function.

As with physical activity, there’s lots of observational data linking diet with Alzheimer’s disease. But no RCTs testing nutrients with cognitive changes. This is that RCT.

Using the infrastructure of another trial investigating macular degeneration in elderly people, researchers randomized more than 3700 participants to get long-chain polyunsaturated fatty acids (LCPUFAs), lutein,
(10 mg)/zeaxanthin (2 mg), and/or placebo in a factorial design. They also got varying combinations of vitamins C, E, beta carotene, and zinc.

Then, at baseline and every two years they were assessed. The main outcome of interest was a composite score of a battery of cognitive function tests. The score could range from -22 to 17.

On that scale, the yearly change for those who received supplements was -0.19 for those who got long-chain polyunsaturated fatty acids and -0.18 for those who did not. Needles to say, this was not a significant difference. Those who received lutein/zeaxanthin had a score change of -0.18 versus -0.19 in those who did not. Again, not significant.

Supplemenation with these nutrients had no effect on cognition.

The accompanying editorial offered some hope because other studies have shown benefits to physical activity:

The FINGER trial reported results of a multifaceted intervention that included diet, exercise, cognitive training, and vascular risk monitoring compared with provision of general health advice in participants aged 60 to 77 years who were at risk of developing dementia. At 2 years, the intervention was associated with significant benefits on a comprehensive neuropsychological test battery.

And they’re right. These studies should be added to others, not replace them. I agree with this, too:

It is likely the biggest gains in reducing the overall burden of dementia will be achieved through policy and public health initiatives promoting primary prevention of cognitive decline rather than efforts directed toward individuals who have already developed significant cognitive deficits.

It seems likely that incorporating physical activity, and maybe even diet, into holistic changes earlier in life are likely to do more to improve health and cognitive decline than waiting until problems have already developed later in life.


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