ARTICLE IN BRIEF
A new report of the National Academy of Sciences, Engineering and Medicine found encouraging but inconclusive evidence that exercise, blood pressure management, and brain training could prevent Alzheimer's disease and dementia.
It would be great if neurologists could hand their patients a detailed plan on how to avoid cognitive decline and dementia. Perhaps the to-do list would include items such as “Walk 30 minutes five times a week” and “do Sudoku puzzle daily.”
But there is no precise prescription for preventing cognitive decline and dementia, according to a thick new report released on June 22 from the National Academies of Sciences, Engineering and Medicine, which undertook an exhaustive review of published research.
At best, for at least for three classes of evidence — brain training, blood pressure management, and exercise — the data are encouraging but inconclusive, according to the report, whose authors noted there was not enough evidence to justify a public health campaign around the three strategies.
“The evidence was not sufficient to give a prescription,” said Sudha Seshadri, MD, FAAN, professor of neurology at Boston University, who served on the report committee. “For now the default might be ‘Do what's good for the rest of your body,’ but we're not at the point of making specific recommendations for preserving brain function.”
THE IMPACT ON PUBLIC HEALTH MESSAGES
The lack of a detailed prevention plan in the voluminous report is likely to confuse and perhaps frustrate patients, who worry about developing dementia and are bombarded with almost daily headlines about tactics for keeping brain health intact.
Richard S. Isaacson, MD, director of the Alzheimer's Prevention Clinic, Weill Cornell Memory Disorders Program at Weill Cornell Medical College/New York-Presbyterian Hospital, said he believes there is a disconnect between the conclusions arrived at in the report, which relied heavily on randomized, controlled trials, and what doctors in practice might rightfully recommend based on a wider array of research, their own clinical experience, and the profile of the patient in their office.
He said he worries that the official report could be interpreted as meaning, “there is nothing you should do. You don't have to exercise, you don't have to eat healthy, you don't have to engage your brain, you don't have to socialize because it won't help your brain.”
Dr. Isaacson said he provides patients with an individualized, detailed plan for reducing the risk of dementia after doing an extensive evaluation of their medical history, lifestyle factors, body composition, blood work and cognitive assessments, though he offers the advice along with some qualifiers.
Marwan Sabbagh, MD, a neurologist who is director of the Alzheimer's Disease and Memory Disorders Division at Barrow Neurological Institute in Phoenix, AZ, said he found the report to be useful, however, because it delineated three strategies for which there is reasonable evidence of benefit — cognitive training, blood pressure management, and physical activity. He noted when a similar systematic review of the research literature was done in 2010 by the Agency for Healthcare Research and Quality there wasn't enough evidence to recommend those strategies, which means there has been some incremental progress in the field of dementia prevention.
“Now we have some general recommendations,” Dr. Sabbagh said. “Though lacking specifics, one-on-one I can use the recommendations to come up with some specifics for my patients,” he said.
He said there is a “measure of encouragement in being able to say, ‘Here is what we know at the moment.’”
While it may take many more years of research to nail down the details, Dr. Sabbagh said that enough is already known to say “It isn't a matter of ‘There is nothing you can do but wait for the inevitable.’”
UPDATING WHAT'S KNOWN
The report by the Academies stemmed from a request by the National Institute on Aging to examine the latest evidence relating to preventing, slowing or delaying the onset of mild cognitive impairment, clinical Alzheimer's-type dementia and age-related cognitive decline, and to make recommendations for public health messaging around prevention. The panel of experts convened for the task was asked to make its recommendations largely on results of randomized, controlled trials, which are considered the gold standard of research but can be difficult and costly to conduct on multifactorial diseases such as dementia and Alzheimer's that can span decades. The panel was also asked to identify areas for future research. [For the report's recommendations, see the sidebar, “Priorities for Research: What's Next?”]
The report, while falling short of a definitive action plan for patients, acknowledged the public's eagerness to find ways to prevent cognitive decline and dementia and said that research suggests “that a window of opportunity exists to prevent or delay the onset of these conditions.”
The report outlined these general recommendations, with the caveat that they weren't supported by high-strength evidence:
* Cognitive training — defined as a broad set of interventions, such as those aimed at enhancing reasoning, memory and speed of processing — to delay or slow age-related cognitive decline. The report said the training could entail a structured computer-based program, or be a stimulating activity such as learning a new language, playing bridge or doing crossword puzzles. The report said, however, there is “no evidence at this time to support a conclusion that cognitive training can prevent or delay mild cognitive impairment or Alzheimer's dementia.”
* Blood pressure management for people with hypertension to prevent, delay, or slow clinical Alzheimer's-type dementia. Managing blood pressure has the added benefit of protecting against cerebrovascular disease and stroke, which can be factors in dementia and Alzheimer's. The report did not specify a specific goal for blood pressure, but noted that “managing blood pressure for people with hypertension, particularly during midlife (ages generally ranging from 35 to 65), is supported by encouraging but inconclusive evidence” when it comes to Alzheimer's-type dementia.
* Increased physical activity to delay or slow age-related cognitive decline. The report noted that physical activity has many other health benefits as well, such as lowering the risk of hypertension, stroke and obesity, and reducing symptoms of depression. But it said that studies fail to demonstrate that increasing physical activity prevents, delays, or slows mild cognitive impairment or Alzheimer's-related dementia. The report did not specify what type of exercise is best or how long or often a person should exercise
Dr. Seshadri, a panel member, said she wished that as a clinician she could give more definitive advice to patients, but she said she thinks it is also important to be frank about what the evidence does and doesn't show and not oversell the potential payoffs of possible interventions.
“For dementia we don't have the evidence beyond the level of suggestion for any specific intervention,” she said. But, on the other hand, “while we don't have incontrovertible evidence that some things work, it doesn't mean that they don't.”
INTERVENTIONS HAVE CONSEQUENCES
Dr. Seshadri, who also is senior investigator and principal investigator of the dementia and stroke studies for the Framingham Heart Study, noted that as the Academies' expert panel put together its report, “There was a recognition that making recommendations, taking actions, are not without consequences.”
She said that is particularly true if the given intervention is costly, such as buying vitamins and supplements or paying for an expensive gym membership or an online brain training program. There are also time considerations. Exercising excessively in the hopes of preventing dementia can come at the expense of spending time with family or friends or pursuing hobbies and other interests.
David Gill, MD, director of the Memory Center at Unity at Rochester Regional Health in New York, said patients might prefer to hear “If you follow these five things your risk of Alzheimer's disease will go down 30 percent.” But he said it's unlikely, no matter the advances in research, that it would be possible to predict any person's fate with certainty.
He said the suggestions in the new report lend support to advice he already gives his patients based on his reading of studies such as the FINGER study, a randomized, controlled trial from Finland that found that targeting diet, exercise, vascular risk factors and brain training slowed cognitive decline in older adults. He said the interplay between vascular disease, stroke and Alzheimer's, while still a subject of debate and study, has to be paid attention to through blood pressure management and other heart-healthy strategies.
The good news for patients is that by being attentive to strategies that may help preserve brain function, he said, adding: “They are going to improve their life overall.”
PRIORITIES FOR RESEARCH: WHAT'S NEXT?
The Academies of Sciences, Engineering and Medicine report identified priorities and strategies for future research, such as begin interventions at younger ages and have longer follow-up; increase participation of traditionally underrepresented populations in studies; include biomarkers as intermediate outcomes; use consistent cognitive outcome measures across trials so that data from different studies came be pooled and analyzed for trends; design studies that can be tested more broadly in clinical practices or community settings. The report listed these questions that need to be answered in future studies.
* Which types of cognitive training are likely to have the greatest impact on age-related cognitive decline? Do structured training programs such as those used in the so-called ACTIVE trial, which was a short-duration intervention that showed some long-lasting effects in certain cognitive domains, improve cognitive performance compared with other cognitively stimulating activities, such as reading or playing cards?
* Which specific intervention elements, or combination of elements, used in the ACTIVE trial are responsible for the observed long-term impact on cognitive performance? (For instance, is group training better than solo?)
* Can cognitive training prevent, delay, or slow mild cognitive impairment or Alzheimer's dementia?
* What is the role of social engagement as part of cognitive training? Does a social aspect make cognitive training more enjoyable and thus have an effect on adherence?
* Are there adverse effects of computer-based cognitive training programs similar to those that have been documented in the computer gaming literature?
BLOOD PRESSURE MANAGEMENT:
* Which populations would benefit most from blood pressure management? Are there some who might be harmed by treatment for hypertension?
* What is the optimal blood pressure management approach at different ages (midlife, late life, very late life)?
* Is there an optimal blood pressure target for cognitive outcomes, and should targets differ among clinical subgroups?
* What is the comparative effectiveness of different classes of antihypertensive treatments (for example, angiotensin II receptor blockers versus other treatments)? Does a focus on blood pressure in isolation from other vascular risk factors limit the impact of cognitive outcomes?
* Which physical activities are most promising for providing cognitive benefits?
* How does the beneficial effect of physical activity vary among subgroups (for instance, people with mild cognitive impairment or people with diabetes)? Are there some groups for which exercise is ineffective or even harmful with respect to cognitive function?
* Are the cognitive benefits or physical activity sustained if the intervention is discontinued?
The report also noted that the following areas, while lacking convincing evidence at the moment, warrant additional research:
* New anti-dementia treatments that can delay or slow disease progression.
* Diabetes treatment
* Depression treatment
* Dietary interventions
* Lipid-lowering treatment
* Sleep quality interventions
* Social engagement interventions
* Vitamin B12 plus folic acid supplementation
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