Plenty of research suggests that physical activity is good for the mind. Prior studies of older adults correlated regular exercise with reduced dementia risk (Larson et al., 2006). Investigations by first author Kirk Erickson, University of Pittsburgh, Pennsylvania, linked aerobic fitness to bigger hippocampi (Erickson et al., 2009) and showed, longitudinally, that walking prevents gray matter loss (Erickson et al., 2010 and ARF related news story).

Randomized trials on the benefits of physical activity are rare, though, as it is hard to get people to stick to a specific exercise regimen (McCurry et al., 2010). One such study on seniors with subjective memory complaints did have promising findings—six months of moderate exercise led to modest improvements on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), measured at 18 months (Lautenschlager et al., 2008 and ARF related news story). The current study, another randomized trial of dementia-free seniors, offers “much more concrete proof” for the idea that exercise helps the brain, said Eric Larson of Group Health Research Institute in Seattle, Washington. “It looked at a biologic endpoint—the size of the part of the brain most important for memory, and one of the parts most affected by dementia”—i.e., the hippocampus.

Collaborating with researchers at Ohio State University in Columbus and Rice University in Houston, Texas, Kramer and Erickson analyzed 120 older adults (average age: 66.5 years) randomized to one year of moderate-intensity walking, or stretching and toning exercises as a control, three times a week. The groups began the study with comparable hippocampal volumes, assessed by magnetic resonance imaging (MRI), and had similar attendance rates. Participants had brain scans, as well as fitness and memory assessments, at baseline, six months, and after the 12-month intervention.

Consistent with the expected 1 to 2 percent annual hippocampal loss in dementia-free seniors (Raz et al., 2005), the control group lost about 1.4 percent volume in this brain region by the end of the 12-month trial. In contrast, the hippocampi of the walkers grew roughly 2 percent. The benefit seemed specific to the anterior part of this brain structure, which mediates acquisition of spatial memory. Similar effects did not appear in the thalamus, caudate nucleus, or posterior hippocampus.

By measuring changes in the participants’ maximal oxygen consumption, the researchers determined that the intervention succeeded in raising aerobic fitness levels, and that larger fitness boosts correlated with greater hippocampal growth. Furthermore, the team found that, within the control group, people with higher baseline fitness levels had less hippocampal shrinkage than those who were less fit, suggesting that fitness protects against loss of brain tissue.

How fitness and hippocampal size correlated with cognition was somewhat nuanced. By the end of the study, the exercise and stretching control groups both showed slight improvement in accuracy and reaction times on a spatial memory task. However, those with better aerobic fitness at baseline and 12 months had better memory performance, as did participants who started or ended the study with larger hippocampi.

To explore possible mechanisms underlying these changes, the authors looked at serum levels of brain-derived neurotrophic factor (BDNF) in blood collected from participants at baseline and 12 months. People who exercise more have higher levels of hippocampal BDNF (Cotman and Berchtold, 2002; Neeper et al., 1995), and increased serum BDNF levels have been correlated with larger hippocampi and better memory performance (Erickson et al., 2010 and ARF related news story). In the present study, greater elevations in serum BDNF were linked to greater gains in hippocampal volume.

All told, the study “attempted to tie together changes in anatomy with changes in blood chemistry with changes in cognition, in a brain region with a pretty well-defined function (episodic memory),” Kramer said.

Among the lifestyle factors proposed to affect cognitive impairment and AD, “the evidence is most persuasive for physical exercise,” commented Ron Petersen of the Mayo Clinic in Rochester, Minnesota, in an e-mail to ARF. “This study supports that contention and lends some anatomical, biomarker support for this position.” In response to the recent declaration by a National Institutes of Health (NIH) expert panel that there is no strong evidence that anything helps prevent AD, some scientists stressed that people should make lifestyle choices that include physical exercise (see ARF related news story).

Of note, participants in the present study had fairly poor cardiovascular fitness and were asked, in the exercise group, to “walk to 60 percent of their maximal heart rate,” Larson said. “This is stuff anybody could do. You’re not getting winded by this level of exercise.”—Esther Landhuis.

Reference:
Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. 2011 Jan 31. PNAS Early Edition. Abstract