Previous observational studies have suggested that both physical activity (see Larson et al., 2006, and Laurin et al., 2001) and mental stimulation (see ARF related news story) can curb the risk of developing dementia. Randomized controlled trials implied a causative effect, reporting that training the brain elevates test scores in the specific areas targeted by training (see ARF related news story), while exercising the body especially improves executive function (see Colcombe and Kramer, 2003). Would the two types of training together work even better? Few studies have investigated that question. In a small trial, researchers reported that two months of both aerobic and mental training improved memory in healthy elderly people more than either alone (see Fabre et al., 2002). On the other hand, a pilot trial found that four months of physical and mental training improved cognitive function no more than single interventions or an educational control (see Legault et al., 2011).

To explore the combined approach, Barnes and colleagues used a 2 x 2 factorial design to compare aerobic activity with stretching and toning and computerized cognitive training with educational videos. The study enrolled 126 older adults who lived on their own and complained of memory or thinking difficulties, but had neither dementia, exercised, or used computers intensively. For three months, half of the participants took three hour-long aerobics classes per week. Active controls spent those hours in stretching and muscle toning classes. Scientists further subdivided those two groups. Three days each week, half played an hour of computer games aimed at improving visual and auditory processing, while the rest watched educational DVDs and answered short questions.

At the beginning and end of the trial, the researchers evaluated verbal learning and memory, verbal fluency, processing speed, executive function, mental flexibility, and visuospatial function. They derived a single composite score for each person by averaging z scores from each test. Z scores are expressed in units of standard deviation (SD) and are comparable to effect size. All groups improved on average by 0.16 SD, but none more than any other. Effect sizes of 0.25-0.3 are considered clinically meaningful, said Barnes, and these data fall below that value. “It’s a small effect size, but these small improvements over the short term could have long-term implications,” said Barnes. “We just don’t know that yet.”

Why did all of the groups improve equally? Since all four exercised both brain and body in some fashion for six hours each week, perhaps time spent doing activities outweighs the importance of what one does exactly, Barnes told Alzforum. Alternatively, stretching and toning could match the potency of aerobic exercise, she said, effectively turning the active control group into an intervention group. Resistance training has improved cognition in previous studies (see Liu-Ambrose et al., 2010). Repeating the tests for cognitive function could also have contributed if the participants merely got better at test taking the second time around, the authors suggested. They added an intervention-free control group by giving cognitive tests to 12 more people and retesting them three months later. Their composite scores nudged up by 0.08 SD, implying that repeated testing explains some of the 0.16 SD uptick seen in the intervention groups.

Social interaction may have played a part, too, Barnes told Alzforum, as both exercise groups worked out in groups at a local YMCA. A previous study reported that socializing boosted brain volume and cognition in a group of elderly Chinese people (see Mortimer et al., 2012). It is also possible that the current study ended too quickly to detect differences, wrote the authors. This sentiment was echoed by Laura Baker, Wake Forest School of Medicine, Winston-Salem, North Carolina. Baker previously found that aerobic exercise enhanced executive function in women more than stretching by six months, but not yet at 12 weeks (see Baker et al., 2010). “Exercise slowly changes and restores health to many systems, so it may take some minimum amount of time for benefits to appear,” she said. A lack of full clinical evaluations and measurements of exercise intensity may have further limited the study, suggested the authors.

These results raise the question of how researchers should design controls. “Often, in the attempt to match intervention and control groups in all aspects except the intervention, there is a risk that not enough contrast exists,” wrote Nicola Lautenschlager, University of Melbourne, Australia, and Kay Cox, University of Western Australia, in an accompanying editorial. Future trials with active controls should run longer to see if a difference arises, Lautenschlager told Alzforum. Similar studies should also include biomarker measurements to root out the underlying biological mechanisms that improve cognition and function, wrote Cox and Lautenschlager.

Upcoming studies are poised to further explore the advantages of aerobic exercise or its combined effects with mental stimulation. An 18-month Alzheimer’s Disease Cooperative Study trial led by Baker and Carl Cotman of the University of California at Irvine will compare stretching to aerobic exercise in 300 sedentary adults with MCI (see ARF related news story). Though these scientists do not plan to include an additional intervention-free control, as Barnes suggests, this paper could cause them to reexamine that decision, said Baker. Additionally, the ongoing 18-month Study of Mental Activity and Regular Training (SMART) trial (see Gates et al., 2011) headed by Maria Singh at the University of Sydney, Lidcombe, Australia, will compare whole-body resistance exercise and computerized cognitive training with seated calisthenics and educational video watching to see if either or both of the more intense interventions more strongly affect global cognitive function and brain morphology in old adults. Several ongoing lifestyle modification trials in Europe also incorporate physical and mental stimulation (see ARF related news story). These trials will be large enough to examine whether multipronged approaches can reduce the incidence of dementia, said Lautenschlager.—Gwyneth Dickey Zakaib.

References:
Barnes DE, Santos-Modesitt W, Poelke G, Kramer AF, Castro C, Middleton LE, Yaffe K. The Mental Activity and eXercise (MAX) Trial: A Randomized Controlled Trial to Enhance Cognitive Function in Older Adults. JAMA Intern Med. 2013 Apr 1:1-8. Abstract

Lautenschlager NT, Cox KL. Can Participation in Mental and Physical Activity Protect Cognition in Old Age? Comment on "The Mental Activity and eXercise (MAX) Trial: A Randomized Controlled Trial to Enhance Cognitive Function in Older Adults." JAMA Intern Med. 2013 Apr 1:1-2. Abstract