Healthy Lives, Healthy Minds: Is it Really True?

Series - Alzheimer's Association International Conference 2014:

A nutritious meal plan, regular exercise, and other behaviors boost mental acuity, according to early results from a 1,260-person study reported at the Alzheimer’s Association International Conference in Copenhagen, Denmark, July 12-17. Miia Kivipelto of the Karolinska Institutet in Stockholm presented the first data out of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability. The FINGER study is a randomized controlled trial that showed a multipart lifestyle intervention improved cognitive scores and, by inference, perhaps curtailed the risk of future Alzheimer’s disease. The large-scale trial stands poised to become the granddaddy of a coming wave of trials to tease out how lifestyle interventions affect dementia susceptibility. Several smaller studies are already ongoing, and researchers shared updates on four trials of exercise and health education programs in a separate symposium at AAIC.

“I was happy to see that in this conference there were many sessions on lifestyle interventions,” Kivipelto told Alzforum. “We need many more studies, we need to understand what is working for different at-risk populations.” In the past, epidemiological studies have indicated that healthy lifestyles protect against dementia. Researchers are only now starting to test that hypothesis directly in clinical trials.

Multi-FINGER Attack
Kivipelto thought it would be insufficient to modify just diet, or just exercise habits, or other single factors in the short term. Instead, the FINGER trial combined multiple interventions. The researchers recruited people aged 60-77 years who they thought could use some help. Specifically, Kivipelto invited people from previous population-based studies who scored high on a calculation of future dementia risk (Kivipelto et al., 2006). Cognitively, the participants performed at or slightly below average on neuropsychological tests.

The participants were randomized to one of two groups: an experimental cohort who received high-intensity interventions, and a control group who received moderate health advice. In that manner, the study was as double-blinded as is possible with lifestyle interventions; control participants still received some encouragement, and the researchers who rated outcomes did not know each subject’s assignment. Lon Schneider, a clinical trialist at the University of Southern California in Los Angeles, praised the study’s design. “This is a real experiment,” he told Alzforum. “The method of selection of patients and the randomization minimized biases.”

Specifically, people in both study arms received advice on how healthy eating, physical activity, mental stimulation, and social activities could abate vascular risk, which is linked to to one’s odds of developing dementia. They underwent blood pressure measurements and weigh-ins three times over the two-year study, and had four blood tests with written advice on their results.

People in the heavy intervention group underwent a much more rigorous regimen. They followed customized diet plans from a nutritionist. Under the guidance of a physiotherapist, they performed strength training and aerobic workouts. They exercised their brains with a computer-based cognitive training program. Several group meetings added social time. In addition, the participants attended more frequent meetings with nurses and physicians to monitor cardiovascular risk factors, such as blood pressure and weight, and received advice on improving those numbers.

The effort paid off, according to Kivipelto’s preliminary results. The two-year intervention period ended earlier this year, and the researchers have calculated their primary outcome measure, a composite score from the standard Neuropsychological Test Battery (NTB). Scores in the intervention group were about 40 percent higher than those in the control segment, Kivipelto said. Specifically, people in the arm with the intensive modifications performed better on tests of memory, executive function, and speed of thought. Kivipelto and colleagues still have plenty of data to analyze, but she told Alzforum that vascular risk factors declined among the intervention group, indicating that their likelihood of future dementia also shrank.

“The magnitude of that composite [NTB] outcome, although some people might say it is small, is certainly as large as what is expected with drugs,” Schneider said. “If this were a drug, the sponsors would be shouting, ‘Breakthrough!’”

Rachelle Doody of Baylor College of Medicine in Houston cautioned in an email to Alzforum that the NTB scores remained in the normal range. “This does not necessarily predict that the same intervention will delay or prevent the development of Alzheimer’s disease,” she wrote. Kivipelto and colleagues plan to follow their study participants for another five years to determine if there will be fewer incident cases of dementia in the intervention group. They will also analyze biomarkers such as Aβ from cerebrospinal fluid (CSF), as well as MRI and PET scans.

Delving into Details
The FINGER trial provides a proof of concept, Kivipelto said: “For sure, now we can say that lifestyle is important.” The study and its combined interventions furnish an ideal example for future work, commented Laura Baker of the Wake Forest School of Medicine in Winston-Salem, North Carolina. Also at AAIC, Baker and three other scientists showed progress reports on their own trials.

Baker has enrolled 50 people in her Piedmont Triad Aging, Cognition, and Exercise Study (PACE). These subjects are at high risk for future dementia thanks to both MCI and prediabetes, a condition in which blood sugar management is abnormal but not yet overtly diabetic. These folks are sedentary and truly need the fitness intervention, Baker told Alzforum. She is always concerned when she sees this MCI/prediabetes combination in her patients. “I know that when I see them in a year, they will have gotten worse,” she said.

The PACE participants undergo either an aerobic training program or a control stretching protocol. With 10 people still in the study phase, Baker said that interim results suggest improved executive function for the aerobic group. Baker is collaborating with Tom Montine at the University of Washington in Seattle to study CSF biomarkers. The people in the aerobic group exhibited reduced CSF tau and phosphorylated tau compared with baseline measurements. “Very few interventions lower tau,” Baker noted. On brain scans, the researchers noted increased blood flow in the anteromedial temporal lobe, a region that the Alzheimer’s Disease Neuroimaging Initiative has shown to be vulnerable in people who are likely to progress to AD.

Like Baker, Nicola Lautenschlager of the University of Melbourne in Australia is targeting sedentary people. With the Individual Goal Setting (INDIGO) trial, Lautenschlager aims to motivate them to exercise. Everyone in her study will receive a customized at-home walking program and regular phone check-ins from volunteer mentors. One motivating factor will be goals, set by the participants, such as being able to play with grandchildren without getting short of breath. Every subject will set goals, but those in the intervention group will regularly discuss their goals with their mentors. Lautenschlager has evaluated 14 of a planned 60 participants thus far. The main outcome will be how well participants keep up their activity, measured by personal records as well as pedometers and accelerometers.

Similarly, Linda Clare of Bangor University in the United Kingdom made goal-setting and mentorship key parts of her intervention. At AAIC, she described a trial within the AgeWell community center in Nefyn, Wales, targeted to people 50 or older. Seniors can partake in various activities such as art, choir, or dancing. In Clare’s trial, 75 participants were evenly split between those who only used the facility, those who also set individual goals in an interview, and those who set goals and received regular telephone mentoring. After a year, physical activity rose in both goal groups, but stayed the same in the controls. People who received mentoring did best.

A physical center like AgeWell may not be a good fit for everyone. Kaarin Jane Anstey of the Australian National University in Canberra is targeting tech-savvy elders with the online Body-Brain-Life program. This 12-week intervention includes seven educational modules on topics such as nutrition and dementia risk factors, and guided activities. Some participants received weekly face-to-face interactions in addition to the computer program. Control participants got regular emails about health topics. In this 176-person study, all groups improved their scores on a questionnaire about AD risk factors. The people who received online plus face-to-face interactions performed the best.

Lifestyle risk research was “left of field” when it emerged 10 years ago, Lautenschlager said, but its heavy presence in Copenhagen showed it has come of age. She and Kivipelto envision a future in which people at risk for dementia receive prescriptions for both medication and lifestyle changes to keep their brains healthy.—Amber Dance

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References

Paper Citations

  1. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 2006 Sep;5(9):735-41. PubMed.

External Citations

  1. Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability

Further Reading

Papers

  1. Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Nissinen A, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and progress. Alzheimers Dement. 2013 Jan 16; PubMed.
  2. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010 Jan;67(1):71-9. PubMed.
  3. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. J Alzheimers Dis. 2010;22(2):569-79. PubMed.
  4. 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.
  5. Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL, . Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2271-81. PubMed.
  6. Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014 Aug;13(8):788-94. PubMed.

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