08.26.2015

Neither moderate physical activity in sedentary older adults nor nutritional supplementation in those with age-related macular degeneration (AMD) had a positive impact on cognitive function, according to two separate studies.

In the first study, participants (ages 70-89) who undertook a 24-month physical activity program showed no difference in scores on the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (adjusted for clinic site, sex, and baseline values) or the revised Hopkins Verbal Learning Test (HVLT-R) versus a control group that underwent health education, reported Kaycee Sink, MD, of Wake Forest University in Winston-Salem, N.C., and colleagues.

The mean DSC task scores were 46.26 points for the physical activity group versus 46.28 for the health education group (95% CI -0.80 to 0.77,P=0.97), and the mean HVLT-R delayed recall scores were 7.22 for the physical activity group versus 7.25 for the health education group (95% CI -0.29 to 0.24, P=0.84), they wrote in the Journal of the American Medical Association.

There was also no difference between the groups in the incidence of mild cognitive impairment (MCI) or dementia, Sink’s group added.

In the second study, older participants (mean age 72.2) who took either long-chain polyunsaturated fatty acids (LCPUFAs) or lutein combined with zeaxanthin had a yearly change in the composite cognitive function score of -0.19 (99% CI -0.25 to -0.13) versus -0.18 (99% CI -0.20 to 0.13) for those in the no-LCPUFAs group, reported Emily Chew, MD, of the National Eye Institute in Bethesda, Md., and colleagues.

In addition, the yearly change in the composite cognitive function score was −0.18 (99% CI −0.24 to −0.11) for participants randomized to receive lutein/zeaxanthin versus −0.19 (99% CI −0.25 to −0.13) for those who did not receive lutein/zeaxanthin, for a difference of 0.03 (99% CI −0.14 to 0.19, P=0.66), they wrote in JAMA.

“Among older persons with age-related macular degeneration (AMD), oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function,” Chew’s group concluded.

But in an accompanying editorial, Sudeep Gill, MD, and Dallas Seitz, MD, PhD, of Queen’s University in Kingston, Ontario, Canada, pointed out that the findings from either of these studies should not be taken as a sign to ignore lifestyle factors when promoting health in older adults.

“Optimizing physical activity should be encouraged at every age — not just when symptoms of cognitive decline appear,” they wrote.

LIFE Trial

The Lifestyle Interventions and Independence for Elders (LIFE) trial enrolled 1,635 sedentary adults at eight U.S. centers from February 2010 until December 2011. All were able to walk 400 m although they were at risk for mobility disability.

Some 818 participants underwent a structured, moderate-intensity physical activity program that included walking, resistance training, and flexibility exercises. The remaining 817 participants received upper-extremity stretching and health education workshops.

Cognition was measured in 1,476 participants (93%) using the DSC task (score range of 0-133 with higher scores indicating better function) and the HVLT-R that included a 12-item word list recall task. Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months.

Incident MCI or dementia occurred in 13.2% of physical activity participants and in 12.1% of health education participants (OR 1.08, 95% CI 0.80 to 1.46), the authors reported.

There were better changes in executive function composite scores in the 307 physical activity patients who were 80 years or older and in the 328 physical activity participants who had a poorer physical performance at baseline than in the health education participants, they found (P=0.01 for interaction for both comparisons).

Since cognitive function remained stable in both groups over the course of the 24 months, Sink said her team “cannot rule out that both interventions were successful at maintaining cognitive function.”

The investigators also noted that they had recruited a population with limited physical ability. “Impaired lower-extremity functioning and the high prevalence of comorbidities may have limited participants’ ability to exercise at sustained levels sufficient to improve cognition,” they wrote.

“Nonetheless, the physical activity group had significantly greater physical activity levels than the health education group, and a more intensive, sustained intervention that could be translatable at the population level would be difficult to achieve,” they stated.

Gill and Seitz acknowledged that the findings from this study differed from previous research that showed a benefit from exercise interventions for improving cognition. They pointed out one reason could be that “the effects of exercise on cognition also may differ in older adults without cognitive concerns (as was the case in the LIFE trial) when compared with individuals with cognitive concerns, MCI, or dementia.”

They added that different neuropsychological tests may be more or less sensitive to cognitive changes that may be influenced by exercise.

AREDS2 Trial

The Age-Related Eye Disease Study 2 (AREDS2) was a double-blind randomized clinical trial, conducted at 82 U.S. academic and community medical centers that included 4,203 participants who were at risk for developing AMD.

In addition to annual eye examinations, validated cognitive function tests were administered at baseline and every 2 years during the 5-year study (October 2006 to December 2012).

The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline in the treated versus untreated participants.

Of the 3,741 participants in the ancillary study, 3,501 (93.6%) underwent cognitive function testing. More than half the participants (57.5%) were female.

There were no statistically significant differences in change of scores for participants randomized to receive supplements versus those who weren’t. The trial evaluated supplementation with LDPUFAs alone, lutein/zeaxathin alone, a combination of the two, or placebo including varying amounts of vitamins C, E, beta carotene, and zinc.

Cognitive outcomes included assessment of the change in a composite of several neuropsychological measures.

The authors also looked for potential interactions between LCPUFAs and lutein/zeaxanthin but did not find any to be significant.

They noted that “worse cognitive function at study entry was associated with increasing age, lower education level, and the male sex in our baseline cross-sectional data.” Other medical risk factors associated with lower cognitive function testing scores included hypertension and other cardiovascular disease, including stroke.

The study had some limitations. Participants “well-nourished and highly educated” with at least intermediate AMD or advanced AMD in one eye. As a result, the findings may not be generalizable. The authors also acknowledged that supplementation may have been undertaken too late in the aging process to make a noteworthy difference.

Gill and Seitz pointed out that other supplements have also failed to turn in significant results in previous studies. However, “promoting a heart-healthy diet such as the Mediterranean diet is more apt to prevent cognitive decline or the onset of dementia than simply prescribing nutritional supplements later in life,” they noted.

No Nihilism

“Although [these] well-designed randomized controlled trials … failed to demonstrate significant cognitive benefits, these results should not lead to nihilism involving lifestyle factors in older adults,” Gill and Seitz wrote. “There is clear evidence that physical activity and healthy diet contribute to improvements in a wide variety of health outcomes.”

Despite the limitations of studies to date, it is likely that diet and exercise have important roles in the prevention of cognitive decline, dementia, and performance of activities of daily living, they said.

However, it’s “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,” they added.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 08.26.2015