No Magic Bullet to Prevent Late-Life Dementia

Megan Brooks

December 19, 2017

There is no proven way to prevent the onset of late-life dementia, results of four systematic evidence reviews conducted by researchers from the Minnesota Evidence-Based Practice Center (EPC) at the University of Minnesota in Minneapolis show.

Investigators summarize findings from randomized controlled trials (RCTs) examining the effectiveness of physical activity, various prescription medicines, over-the-counter vitamins and supplements, and cognitive training in preventing the development of cognitive decline, mild cognitive impairment (MCI), and clinical Alzheimer-type dementia.

The reviews were published online December 18 in Annals of Internal Medicine.

"We looked at drugs. We looked at over-the-counter vitamins and supplements. We looked at exercise. We looked at cognitive training. And overall, the results didn't show much benefit," study investigator Howard Fink, MD, MPH, from the Geriatric Research Education and Clinical Center, VA Health Care System, Minneapolis, said in an Annals podcast.  However, one study that combined cognitive training, exercise, and diet did show "some improvement in cognitive outcomes," he said.

"When we looked at the evidence for group cognitive training, what we found was that people improved in the areas that they trained in, but that training did not extend to other areas. So, for example, if you trained in processing speed, there wasn't an improvement in memory," said co-investigator Mary Butler, PhD, from the Division of Health Policy and Management, University of Minnesota.

Aim for a Healthy, Active Life

For prevention of late-life dementia, "there's no magic bullet," said Dr Butler. "But those areas that we did find potentially, some positive findings, they are very consistent with public health types of messages that we hear all the time. Live a healthy life, eat a good diet, stay cognitively active and engaged socially."

With funding from the Agency for Healthcare Research and Quality, the EPC researchers took a critical look at the literature to determine whether any interventions had enough quality evidence to warrant a recommendation.

For physical activity, they reviewed data from 16 RCTs comparing a physical activity intervention with an inactive control. The evidence was "insufficient" for drawing conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. "Low-strength" evidence showed that a multicomponent intervention that included physical activity, diet, and cognitive training improved several cognitive outcomes, they report.   

The researchers reviewed data from 51 unique RCTs comparing the efficacy of various pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. The trials were rated as having a low to moderate risk of bias. The evidence did not support use of any of the studied pharmacologic treatments (dementia medications, antihypertensive agents, diabetes medications, nonsteroidal anti-inflammatory drugs or aspirin, hormones, and lipid-lowering agents) for cognitive protection in persons with normal cognition or MCI, the authors report.   

The review of cognitive training included 11 trials of adults with normal cognition or MCI at baseline. The trials had low to medium risk of bias. Cognitive training was mostly computer based for healthy adults and was done in group sessions for those with MCI. 

For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence), the researchers report. For individuals with MCI, cognitive training did not appear to affect performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient.  

The fourth review looked at 38 trials with low to medium risk of bias that compared over-the-counter (OTC) supplements, including omega-3 fatty acids, soy, Ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, or multi-ingredient supplements, with placebo or other OTC interventions for preventing or delaying cognitive decline, MCI, or clinical Alzheimer-type dementia. This review showed "insufficient" evidence to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI.  

"Humbling" Results >

"The risk of Alzheimer's may be affected by a lot of different factors, and these studies attempted to intervene on those factors and didn't find a real big effect. So, it's a humbling result [and] tells us that we have a lot to learn," said Dr Fink.

"In part, the lack of evidence reflects the challenge of studying prevention of a common chronic disease that originates well before symptoms occur," writes Eric Larson, MD, MPH, Kaiser Permanente Washington Health Research Institute in Seattle in an editorial.

"To see effectiveness, trials on preventive interventions may need to begin when participants are in midlife. Such lengthy trials would have huge logistic challenges, be costly, and be difficult to interpret because of probable selective attrition," he notes.  "Equally challenging," says Dr Larson, is that many of the most promising interventions, such as controlling hypertension, avoiding smoking, exercising, and treating diabetes and other vascular risk factors, are already goals of standard medical care. "The need for randomization to control treatments would create ethical dilemmas. Another reason for the disheartening findings of the EPC papers is that they reviewed only RCTs."

Encouraging Observational Data

Other studies have found some evidence that following a healthy lifestyle earlier in life may help protect against dementia.

For example, the large FINGER study from Finland, which was reported in 2014, showed that a group undergoing a healthy lifestyle intervention (including nutritional guidance, physical activity, cognitive training, and management of cardiac risk factors) had less cognitive decline than the group that received just regular health advice.

In 2015, the Alzheimer's Association published an evidence review of lifestyle behaviors and how they might affect brain health, which led the organization to release "10 Ways to Love Your Brain," which lists factors that can reduce cognitive decline and may reduce dementia. 

At the 2017 Alzheimer's Association International Conference, a comprehensive report from The Lancet Commission on Dementia Prevention, Intervention and Care concluded that the best chance for preventing dementia is a "life course" approach, particularly toward suspected modifiable risk factors.

The report found that more than one third of global dementia cases may be preventable by addressing nine lifestyle factors that affect an individual's risk. These factors are completing secondary education in early life; hypertension; obesity and hearing loss in midlife; and smoking, depression, physical inactivity, social isolation, and diabetes in later life.

"The evidence has started to mount that lifestyles can change your risk for cognitive decline and various dementias," Dean Hartley, PhD, director of science initiatives at the Alzheimer's Association, noted in an interview with Medscape Medical News. "We are still looking for that full evidence-based information but in aggregate there is a lot of good news. There are things people can do now to lower their risk of dementia and promote brain health. Things like exercise, cognitive training, but also managing comorbidities like diabetes, hypertension and high cholesterol."

In 2018, the Alzheimer's Association will begin recruiting for the US Protect Through a Lifestyle Intervention to Reduce Risk (US POINTER) study, a 2-year clinical trial to test whether lifestyle intervention focused on combining physical activity, healthy nutrition, social and intellectual challenge and improved self-management of medical conditions can protect cognitive function in older adults who are at increased risk for cognitive decline.

What to Tell Patients

In his editorial, Dr Larson notes that when people ask him how to prevent dementia, they often want a simple answer, such as vitamins, dietary supplements, or the latest hyped idea. What does he tell them?

"I tell them that they can take many common-sense actions that promote health throughout life and may help to avoid or delay ADRD [Alzheimer's disease and related dementias], namely regular physical activity; control of vascular risk factors, including preventing or effectively managing diabetes; not smoking; and maintaining a healthy diet and weight. Engaging in cognitively stimulating activities and avoiding social isolation also are probably beneficial," writes Dr Larson.

As patients age, it's also important to correct vision and hearing loss and steer clear of drugs that harm the brain and increase dementia risk, such as chronic high doses of anticholinergics.

It's important to note, concludes Dr Larson, that "none of these recommendations has harmful side effects."

The Agency for Healthcare Research and Quality provided primary funding for the reviews. The authors and Dr Larson have disclosed no relevant financial relationships.

Ann Intern Med. Published online December 18, 2017. Physical activity review, Pharmacologic intervention review, Cognitive training review, OTC supplement review, Editorial

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