Of all the diseases that afflict people in old age, people fear Alzheimer’s most. How can they protect themselves? A report from the National Academies of Science, Engineering, and Medicine (NASEM) acknowledges some possible steps, but stops short of issuing concrete recommendations. They base their report on a thorough review of the literature that finds modest but inconclusive evidence that cognitive training, blood pressure management, and regular physical activity prevent or delay cognitive decline. However, the data are still too weak to issue specific guidelines to the general public, wrote the committee of senior scientists led by Alan Leshner, CEO emeritus of the American Association for the Advancement of Science, and Story Landis, director emeritus of the National Institute of Neurological Disorders and Stroke.

“The evidence has not yet matured to the level that would support an assertive public health campaign,” the authors wrote. However, “the report does identify those interventions, supported by some evidence of benefit, that … should be discussed with [people] who are actively seeking advice on steps they can take to maintain brain health as they age.”

“It’s a very balanced report that truly reflects the level of evidence currently available,” said Edo Richard, Radboud University, Nijmegen, Netherlands, who did not contribute to the report apart from presenting at a workshop that helped inform it. “We should always be open and honest with patients and the general public, so cannot tell people that by doing this they will prevent cognitive decline. We do not know.”

An NIH report in 2010 argued that there wasn’t sufficient evidence to recommend any intervention to prevent cognitive decline or dementia (see May 2010 news). Since then, researchers have published more clinical trials, and have chipped away at the mechanisms underlying dementia pathology. In 2015, the National Institute on Aging commissioned the Agency for Healthcare Research & Quality (AHRQ) to review the latest evidence on prevention and write a report on what they found. The NIA then asked the NASEM to put together a committee of experts to review the report and make recommendations for public health messaging and future research.

Based on the AHRQ report, the NASEM committee highlights three areas where evidence is encouraging but inconclusive. The first is cognitive training, where a large, 10-year, randomized trial called ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) provided modest evidence that over time, an interactive intervention improved long-term cognitive function and helped people stay independent in their daily activities, provided they started out with normal cognition. No evidence yet suggests that training helps prevent or delay mild cognitive impairment or Alzheimer’s disease, they wrote.

Blood pressure control in midlife may also be helpful. Treating hypertension prevents stroke and cardiovascular disease—both risk factors for AD—and a majority of dementia patients have some sign of these. Though clinical trial results disagree, prospective cohort studies and understanding of the cerebrovascular contribution to disease mechanisms suggest that controlling blood pressure could be protective. These authors deem this enough evidence to suggest careful management of blood pressure as a way to prevent, slow, or delay Alzheimer’s.

Lastly, they point to exercise as a possible protective factor. Many, but not all, clinical trials suggest it can reduce age-related cognitive decline. Positive trials take added support from prospective cohort studies and known biological mechanisms underpinning Alzheimer’s.

Leshner and colleagues suggest this information be featured on the NIH website and other publicly accessible outlets. That way, it can inform people who are interested in bettering their chances of healthy brain aging. They also support clinicians working cognitive benefits into their patient conversations when they prescribe these interventions for other conditions. Even so, the evidence remains too weak to warrant a broad-based public health campaign, the authors said. Richard brought up the added argument that since many of these studies, particularly the randomized controlled trials, sample from selected populations, it’s questionable whether their results would generalize to the public at large.

How can researchers build a stronger case for prevention? More and better-quality randomized controlled trials, the committee wrote. Consistent results in those would increase their confidence. They recommend that the National Institutes of Health invest more money in this type of research. They also urge researchers to compare different types of cognitive training, blood pressure therapy, and exercise, to see which are most effective. In addition, studies must include more diverse racial, ethnic, and socioeconomic groups; studies should start when people are younger and follow them longer. Incorporating biomarkers could greatly improve these trials, they wrote. Recruiting people at higher risk for decline is also important, as is harmonizing cognitive outcomes across studies so scientists can pool results.

Aside from the three interventions recommended in this report, the authors suggest scientists conduct randomized controlled trials on additional interventions that are supported by either observational and risk-factor studies or that make sense biologically. Possibilities include new anti-dementia, diabetes, depression, or lipid-lowering treatments; sleep and social-engagement interventions; and vitamin B12 plus folic acid supplements. The authors call out hormone replacement therapy, vitamin E, and gingko biloba as having no evidence of benefit.—Gwyneth Dickey Zakaib

Comments

Make a Comment

Comments on this content

  1. I am disturbed that this new report from the National Academies of Science, Engineering, and Medicine has concluded that an “assertive public health campaign” cannot yet be offered for dementia prevention. They are correct that definitive evidence is not currently available to document the value of preventive measures in preventing late-life dementing illnesses. But the absence of evidence is not evidence of absence! We already know that hypertension is linked to stroke, and that stroke contributes to cognitive impairment in Alzheimer’s disease. We also know that periodontitis is a risk factor for heart disease and stroke (and perhaps AD). Low levels of physical activity and obesity are also risk factors for heart disease and stroke. Who exactly would be harmed by a public health campaign recommending high levels of physical and mental activity; dental care; avoidance of head injury, obesity, and smoking; control of diabetes and hypertension; and a low-fat, high–fiber diet? 

    References:

    . A Modest Proposal for a Longitudinal Study of Dementia Prevention (with apologies to Jonathan Swift, 1729). J Alzheimers Dis. 2012 Sep 17; PubMed.

  2. There will never be the volume nor the quality of intervention studies that show main effects and complex interactions needed to “prove” that lifestyle factors affect the incidence of dementia/AD. Rather than dismiss observational research, we must recognize that longitudinal cohort studies may actually provide more evidence than traditionally thought, given the length of time it takes to develop AD (i.e., from conception on!). This thesis is fully developed in our book, "Alzheimer's Disease: Life Course Perspectives on Risk Reduction.” 

    Clinical trials also have a range of methodologic shortcomings that are not easily overcome, not the least of which is the relatively short follow-up time that most trials necessitate. Advancements in the U.S. in this field lag behind Europe and Scandinavia, where multi-armed prevention trials in populations are ongoing. In the U.S., there is little attention being focused on such prevention trials, with funding being tied up with expensive treatments and diagnostic techniques. There should be a marriage of these two approaches in order to maximize “going deep” with “going wide” and gaining external validity on a population level.

    And I agree with Robert Friedland: What possible harm could be done by recommending heart- and brain-healthy lifestyles?

Make a Comment

To make a comment you must login or register.

References

News Citations

  1. NIH Calls for More (and Different) Research on Preventive Measures

External Citations

  1. AHRQ report
  2. hypertension

Further Reading

Papers

  1. . Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer's Disease. J Alzheimers Dis. 2017;58(4):1089-1097. PubMed.

Primary Papers

  1. . Preventing Cognitive Decline and Dementia: A Way Forward. Washington (DC): National Academies Press (US); 2017 Jun. The National Academies Collection: Reports funded by National Institutes of Health.