05 Sep 2008

Hopping off the couch and into the gym helps both heart and mind, even in seniors at risk for dementia. Backed thus far by descriptive studies, this claim now has “proof of concept” from research published in this week’s JAMA. In a randomized, controlled trial of 138 older adults with subjective memory complaints but no diagnosed dementia, Australian researchers report that a 24-week moderate exercise program improved mental function gauged at 18 months using the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), a 70-point scale of 11 cognitive tests. Though the gain was modest—a 0.69-point separation between treatment and control groups in ADAS-Cog changes from baseline—the authors say their study demonstrates “the potential benefit of a simple intervention that is almost universally available.” The treatment response might be associated with APOE genotype: post-hoc analysis showed that ADAS-Cog improvements among APOE4 non-carriers in the exercise group were significantly better than those of participants in the other groups combined.

In large observational studies, physically active elders have fared better on cognitive tests (Weuve et al., 2004) and had reduced rates of dementia compared with more sedentary peers (Abbott et al., 2004). First author Nicola Lautenschlager of the University of Melbourne, and other Australian collaborators, set out to test whether this mind-body link would hold up in a single-site randomized trial. In other words, could a modest dose of physical activity slow rates of cognitive decline in seniors at increased AD risk? The researchers recruited volunteers (mean age ~69) who reported memory difficulties but did not have clinically diagnosed dementia, depression, or chronic mental illness. People with life-threatening medical conditions or poor English fluency were excluded. Among 311 individuals screened by phone, 170 eligible participants were randomized to one of two groups, exercise or control, of which 138 completed the 18-month trial. The control group received educational material about memory loss, stress management, diet, alcohol, and smoking but not about physical activity. People in the exercise group got these materials, too, and were encouraged to do at least 150 minutes—in three 50-minute sessions—of moderate-intensity exercise each week through an individualized, home-based program developed with a trained staff member. Most participants chose walking or other aerobic exercise, and about one in seven included light strength training. To monitor progress and ensure compliance in the exercise regimen, participants had on average two structured phone interviews during the 24-week intervention.

At six, 12, and 18 months, all study participants were assessed for level of physical activity, cognitive function, mood, and quality of life. Researchers noted 10 adverse events—two among control subjects, eight in the intervention group—during the study, but none were judged to be a direct consequence of the exercise program.

Starting from the same mean ADAS-Cog scores at baseline (7.0 points for both groups), the exercisers improved an average of 0.73 points over 18 months, versus 0.04 points among control subjects—a 0.69-point spread. Though modest, the observed effect of moderate exercise on cognition in this trial is encouraging, the authors emphasize, noting the failure of pill-popping interventions to show significant cognitive benefit in randomized trials of seniors with mild cognitive impairment (MCI). Notably, a clinical trial involving 769 MCI patients found that neither donepezil nor vitamin E fared much better than placebo pills in their effects on conversion to dementia and changes in cognitive test scores when taken daily over a three-year period (see ARF related news story).

In an accompanying editorial, Eric Larson of Group Health Center for Health Studies in Seattle, Washington, notes—and the authors concur—that the study participants were much younger than the population at highest risk for AD, calling into question the clinical significance of the findings. “To assess the true value of this intervention in reducing cognitive decline, a study enrolling a higher proportion of older adults should be conducted,” Larson writes. “In older populations, prevalence of mild cognitive impairment is highest, cognitive decline occurs more commonly, and dysfunction caused by dementia is most important from personal and public health perspectives.”

Even if the exercise effects are meaningful, the greater challenge is how to encourage increased physical activity over the long haul, wrote Larson in an e-mail to ARF. In the new study, 78.2 percent of the exercise group participants adhered to the prescribed intervention over the 24 weeks. By six months, only 25 percent of exercisers achieved the study’s target physical activity level (70,000 steps or more per week), versus 17.6 percent of control subjects reaching this goal. The trend held at 12 months, with 29.4 percent of exercisers (versus 17.6 percent of control subjects) meeting the target. By 18 months, however, the exercisers had lost their edge such that the proportion meeting the physical activity target was equal (18.8 percent) for both groups.

In post-hoc analyses, the researchers found that changes in ADAS-Cog scores across the study duration were significantly greater among APOE4 non-carriers in the physical activity group compared with individuals in the other groups combined. Therefore, they argue, “it is possible that the cognitive benefits associated with physical activity in this trial were attenuated by pre-existing or ongoing deleterious effects of APOE4.”—Esther Landhuis

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References

News Citations

1. Early Intervention Trial Bears Little Fruit, but Sows Hope 15 Apr 2005

Paper Citations

1. Weuve J, Kang JH, Manson JE, Breteler MM, Ware JH, Grodstein F. Physical activity, including walking, and cognitive function in older women. JAMA. 2004 Sep 22;292(12):1454-61. PubMed.
2. Abbott RD, White LR, Ross GW, Masaki KH, Curb JD, Petrovitch H. Walking and dementia in physically capable elderly men. JAMA. 2004 Sep 22;292(12):1447-53. PubMed.
3. Larson EB. Physical activity for older adults at risk for Alzheimer disease. JAMA. 2008 Sep 3;300(9):1077-9. PubMed.

Other Citations

1. donepezil

External Citations

1. APOE

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.
2. Santana-Sosa E, Barriopedro MI, López-Mojares LM, Pérez M, Lucia A. Exercise training is beneficial for Alzheimer's patients. Int J Sports Med. 2008 Oct;29(10):845-50. PubMed.
3. 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.

News

1. Sorrento: More Fun, Less Amyloid for Transgenic Mice 18 Mar 2005
2. Early Intervention Trial Bears Little Fruit, but Sows Hope 15 Apr 2005