To anyone who’s aware that efforts to develop Alzheimer’s drug treatments have met failure after failure, and to have therefore decided that prevention is the only hope, a U.S. panel of experts issued a sobering message on Thursday: Don’t count on it.
From physical activity to avoiding high blood pressure to brain training, a 17-member committee assembled by the National Academies of Sciences concluded, no interventions are “supported by high-strength evidence.” Instead, some high-quality studies found that one or another intervention worked, but other equally rigorous studies found they didn’t.
Three that the report focused on were cognitive training, blood pressure control, and physical activity.
1. Cognitive training
The evidence for programs aimed at boosting reasoning, problem-solving, memory, and speed of processing does include randomized trials that reported benefits from brain training, but the report calls that evidence “low to moderate strength.” One problem: There seemed to be benefits for two years, but not after five or 10. Results in other randomized studies were even more equivocal. There are also data from studies that are less rigorous, leading the committee to conclude that brain training (computer-based or not) can delay or slow age-related cognitive decline — but not Alzheimer’s.
2. Controlling blood pressure
Evidence that this helps is weaker still. It’s mostly not based on randomized controlled trials, but the committee decided there is “sufficient” evidence from other kinds of studies as well as from understanding how the brain works to conclude that managing hypertension (especially from ages 35 to 65) can prevent, delay, or slow Alzheimer’s disease, and therefore to include it in public health messages. But there’s no good evidence on how best to reduce high blood pressure; of all the kinds of drugs that do so, however, angiotensin receptor blockers seem to be the best for cognition, for unknown reasons.
3. Physical activity
Evidence for this is on a par with that for blood pressure: “evidence is insufficient to conclude whether increasing physical activity” prevents or slows Alzheimer’s. Randomized controlled trials only sometimes showed benefit, though there is some evidence from other kinds of studies shows that exercise delays or slows age-related cognitive decline (but not Alzheimer’s).
“Even though clinical trials have not conclusively supported the three interventions,” Alan Leshner, chair of the committee and CEO emeritus of the American Association for the Advancement of Science, said in a statement, “the evidence is strong enough to suggest the public should at least have access to these results to help inform their decisions.”
The need for prevention strategies
The disappointing conclusion comes in the wake of a review published last month of the 105 experimental anti-Alzheimer’s compounds in development. It concluded that their immediate prospects are so poor that the U.S. is unlikely to meet its goal of having a “meaningful” therapy for Alzheimer’s by 2025. That makes the need for prevention strategies greater than ever.
Some experts outside the committee said it had set too high a bar. Henry Mahncke, CEO of brain-training company Posit Science, criticized the committee for lumping together all kinds of cognitive training. That diluted the results showing that the kind that taps into neuroplasticity, the brain’s ability to change its structure and function, “consistently works,” while other forms have “poor to mixed results.”
The Alzheimer’s Association said it is sticking with its “10 Ways to Love Your Brain” and reduce the risk of dementia. The 10 include physical activity, lifelong learning, heart health, and sound sleep. “No one is promising this is going to prevent Alzheimer’s,” said spokesman Niles Frantz, “but we think there is enough evidence to say it can reduce your risk.” Unlike the committee, he said, “we believe it is worth talking publicly about these things.”
The neurobiology of dementia suggests that “a multifaceted approach [to prevention] may be most effective,” the report notes. But it is fiendishly complicated to do randomized controlled trials on more than one intervention at a time.
However, STAT has learned, a large-scale, U.S.-based lifestyle intervention study to prevent cognitive decline and dementia will be introduced at the Alzheimer’s Association International Conference in London in July. It is expected to be modeled on a Finnish study that found that a kitchen sink approach — healthy eating, brain training, exercise, and managing diabetes and cardiovascular risk — slows cognitive decline.