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.
The report can be download for free, though email registration is required.—Gwyneth Dickey Zakaib
- Dougherty RJ, Schultz SA, Kirby TK, Boots EA, Oh JM, Edwards D, Gallagher CL, Carlsson CM, Bendlin BB, Asthana S, Sager MA, Hermann BP, Christian BT, Johnson SC, Cook DB, Okonkwo OC. 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.