There are no proven interventions with enough quality evidence to warrant a recommendation for preventing cognitive decline or Alzheimer’s dementia, according to a team of researchers from the Minnesota Evidence-based Practice Center (EPC).
A new meta-analyses of four systematic reviews suggested that there is not enough definitive evidence on the link between physical activity, prescription medications, over-the-counter vitamins and supplements, or cognitive training interventions and preventing late-life dementia, reported Howard Fink, MD, MPH, also of the VA Health Care System in Minneapolis, and colleagues online in the Annals of Internal Medicine.
“Overall the results didn’t show much benefit,” Fink told MedPage Today. “Based on a comprehensive review of the medical literature, primarily focused on randomized controlled trials, but also based on a search for quasi-experimental observational studies, we found little to no benefit for the effectiveness of interventions to protect against cognitive decline and dementia.”
Writing in an accompanying editorial, Eric B. Larson, MD, MPH, of Kaiser Permanente Washington Health Research Institute in Seattle, Washington, who was part of the National Academy of Medicine committee, commented that “to put it simply, all evidence indicates that there is no magic bullet.”
He explained that the NAM committee searched for convincing evidence of effective preventive interventions and although they “found some intriguing positive results for physical activity, cognitive training, and possibly multifactorial interventions, nothing even approached the evidence level required for a USPSTF recommendation.”
In their systematic review, Fink and colleagues reviewed data from 16 trials which compared physical activity interventions — aerobic training, resistance training, and tai chi — with an inactive control. While they found insufficient evidence to draw conclusions about the effectiveness of short-term, single-component interventions, they did find low-strength evidence that combining different types of interventions at the same time — such as physical activity, diet, and cognitive training — yielded some improvement in cognitive outcomes.
Results from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial showed that of 1,260 adults ages 60 to 77 years with CAIDE (Cardiovascular Risk Factors, Aging and Dementia), those who received an intervention with physical activity, diet, and cognitive training saw a 25% greater 2-year improvement in multi-domain neuropsychological test performance compared with controls.
Analysis of 11 trials of adults with either normal cognition or mild cognitive impairment at the time of enrollment found insufficient evidence that cognitive training exercises could prevent dementia.
While cognitive training seemed to offer some protection among otherwise healthy older adults in the domain of training, it did not offer broader cognitive or functional benefit. Among five trials of adults who already had mild cognitive impairment or other subjective memory, three found no statistically significant effects of the training and two small trials found mixed results of training on cognitive testing outcomes.
“When we looked at the evidence for group cognitive training, what we found was that people improved in areas that they trained in but that training did not extend to other areas,” stated co-author Mary Butler, PhD, MBA. For example, memory training improved memory but not any other aspects of cognition.
Prescription Medication and Over-the-counter Vitamins and Supplements
Analysis of more than 50 trials comparing the effect of prescription medication with placebo, usual care, or active control on cognitive outcomes suggested that studied pharmacologic treatment had no cognitive protection among people with normal cognition or mild cognitive impairment. Such treatments included dementia medications, antihypertensives, diabetes medications, NSAIDs or aspirin, hormones, and lipid-lowering agents.
Adverse events were inconsistently reported but were more common for estrogen (stroke), estrogen–progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism), noted Fink and his team.
Similarly, 38 trials comparing over-the-counter vitamins and supplements — such as omega-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or beta carotene, multi-ingredient supplements — with placebo or other interventions found insufficient evidence to suggest that any of the supplements lowered the risk for cognitive decline.
Fink and colleagues concluded that over-the-counter supplements may work better in people with insufficient intake or levels of the nutrient or vitamin and that “more and larger trials that test effects of supplements and use clinically important outcomes are urgently needed.”
The report from Fink and colleagues followed a study from the National Academies of Science, Engineering, and Medicine earlier this year which said that three interventions — cognitive training, blood pressure management in those with hypertension, and increased physical activity — had “inconclusive but encouraging” evidence that they can help stave off dementia. Shortly after, the Alzheimer’s Association International Conference highlighted press briefings with a focus on disentangling disease risk factors, rather than randomized controlled drug trials.
Although the reasons for the report findings were not entirely clear, Fink noted that possible explanations could be that they simply don’t work or that the studies started the interventions too late in life or didn’t use them long enough.
“It’s difficult to interpret what a failure or a no finding really suggests. The studies themselves had problems with how they were conducted … it’s difficult for us to really say perhaps we might have found something more positive if they ran them for a long period of time or differences in how they were conducted,” explained Butler.
“While we cannot rule out the possibility that some of these interventions could have cognitive benefits, this is theoretical and the available evidence does not support this and does not justify their use for the sole purpose of protecting against cognitive decline and dementia,” agreed Fink.
The research was funded by the Agency for Healthcare Research and Quality.
Jutkowitz reported grants from AHRQ outside the submitted work. Ratner, Hemmy, and Barclay reported grant support from AHRQ during the conduct of the study.
F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner