Get Moving—Walking Enlarges Hippocampus, Preserves Memory in Seniors

Listen up, seniors. In a randomized trial of 120 of your sedentary peers, 40 minutes of walking, three times a week for a year, brought measurable benefit in the form of bigger brains and improved spatial memory. “To get such dramatic results from a few hours a week was somewhat surprising,” said senior investigator Arthur Kramer of the University of Illinois, Champaign-Urbana, in an interview with ARF. He and colleagues reported the findings online January 31 in the Proceedings of the National Academy of Sciences USA.

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

Comments

  1. This work very much concords with our PNAS paper, which found that exercise causes a selective increase in dentate gyrus CBV (Pereira et al., 2007).

    One thing to note is that they find that the increase in hippocampal volume correlates with exercise-induced increases in serological BDNF. Interestingly, previous studies have documented that within the hippocampus, exercise causes a selective upregulation of BDNF expression in the dentate gyrus and CA3. Thus, although Erickson et al. did not assess individual hippocampal subregions, it is plausible to assume that the effect they are seeing is really driven by exercise-induced changes in the dentate gyrus. Indeed, in the discussion section, the authors suggest this as the driving mechanism.

    We and others have found that the dentate gyrus is differentially affected by "normal aging" and relatively preserved in AD. This is one reason I think that exercise will be most beneficial for cognitive aging and less so for AD (which more prominently targets other hippocampal subregions).

    References:

    Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5638-43. PubMed.

    View all comments by Scott Small

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References

News Citations

  1. Research Brief: To Preserve Your Gray Matter, Take a Hike
  2. Work Up a Sweat to Stay Sharp, Randomized Trial Suggests
  3. Research Brief: BDNF Data Speak Volumes, Offer Therapeutic Target
  4. NIH Calls for More (and Different) Research on Preventive Measures

Paper Citations

  1. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006 Jan 17;144(2):73-81. PubMed.
  2. Erickson KI, Prakash RS, Voss MW, Chaddock L, Hu L, Morris KS, White SM, Wójcicki TR, McAuley E, Kramer AF. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus. 2009 Oct;19(10):1030-9. PubMed.
  3. Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, Gach HM, Thompson PM, Ho AJ, Kuller LH. Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology. 2010 Oct 19;75(16):1415-22. PubMed.
  4. McCurry SM, Pike KC, Logsdon RG, Vitiello MV, Larson EB, Teri L. Predictors of short- and long-term adherence to a daily walking program in persons with Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2010 Sep;25(6):505-12. PubMed.
  5. Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, Greenop KR, Almeida OP. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 2008 Sep 3;300(9):1027-37. PubMed.
  6. Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD. Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex. 2005 Nov;15(11):1676-89. PubMed.
  7. Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002 Jun;25(6):295-301. PubMed.
  8. Neeper SA, Gómez-Pinilla F, Choi J, Cotman C. Exercise and brain neurotrophins. Nature. 1995 Jan 12;373(6510):109. PubMed.
  9. Erickson KI, Prakash RS, Voss MW, Chaddock L, Heo S, McLaren M, Pence BD, Martin SA, Vieira VJ, Woods JA, McAuley E, Kramer AF. Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J Neurosci. 2010 Apr 14;30(15):5368-75. PubMed.

Further Reading

Papers

  1. Teri L, Gibbons LE, McCurry SM, Logsdon RG, Buchner DM, Barlow WE, Kukull WA, LaCroix AZ, McCormick W, Larson EB. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003 Oct 15;290(15):2015-22. PubMed.

Primary Papers

  1. 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. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22. PubMed.

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