No interventions proven to prevent late-life dementia, systematic reviews find

There is no proven intervention for preventing late-life dementia, according to four systematic reviews examining trials of various interventions.

Researchers from the Minnesota Evidence-based Practice Center (EPC) reviewed published research to determine whether physical activity, prescription medications, over-the-counter (OTC) vitamins and supplements, or cognitive training interventions could help prevent dementia in patients who did not have it when the studies were done. The reviews were funded by the Agency for Healthcare Research and Quality and the National Institute on Aging.

The vast majority of research showed that none of the interventions were effective. Findings were published Dec. 19 by Annals of Internal Medicine.

For physical activity, researchers reviewed data from 16 trials with low to moderate risk of bias that compared a physical activity intervention with an inactive control. Most trials had six-month follow-up, while a few had one- or two-year follow-up. The reviewers found insufficient evidence to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. They did find low-strength evidence that combining different types of interventions at the same time, such as physical activity, diet, and cognitive training, improved cognitive test performance.

For prescription medications, researchers reviewed data from 51 trials with low to moderate risk of bias comparing the effect of prescription medication with placebo, usual care, or active control on cognitive outcomes. The trials reviewed three dementia medications, 16 antihypertensive agents, four diabetes medications, two NSAIDs or aspirin, 17 hormones, and seven lipid-lowering agents. The evidence did not support use of any of the treatments for cognitive protection in persons with normal cognition or mild cognitive impairment.

For cognitive training, 11 trials with low or medium risk of bias, six enrolling healthy adults with normal cognition and five enrolling adults with mild cognitive impairment, provided insufficient evidence that cognitive training exercises could prevent dementia. Trainings for healthy older adults were mostly computer based; those for adults with mild cognitive impairment were mostly group sessions. For healthy older adults, training improved cognitive performance in the domain trained (e.g., memory) but not in other domains (moderate-strength evidence). Results for populations with mild cognitive impairment suggested no effect of training on performance (low-strength and insufficient evidence).

For OTC vitamins and supplements, a review included 38 trials comparing OTC supplements, including 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 OTC interventions for preventing or delaying cognitive decline, mild cognitive impairment, or clinical Alzheimer-type dementia. The reviewers found insufficient evidence that any of the supplements reduced the risk for cognitive decline.

Daily folic acid plus vitamin B₁₂ was associated with statistically significant improvements in performance on some objectively measured memory tests, but these improvements were considered of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, beta-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength. Adverse events were rarely reported.

According to the researchers, it is not entirely clear why these four categories of interventions failed. They noted that while there was no evidence about whether an intervention to practice a healthy lifestyle earlier in life protects against cognitive decline or dementia in later life, it is unlikely to worsen cognition and may have other, noncognitive benefits.

An editorial said that there is no “magic bullet” for preventing dementia. “When people ask me how to prevent dementia, they often want a simple answer, such as vitamins, dietary supplements, or the latest hyped idea. I tell them that they can take many common-sense actions that promote health throughout life and may help to avoid or delay [Alzheimer 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,” the editorialist wrote. “Engaging in cognitively stimulating activities and avoiding social isolation also are probably beneficial. As our patients age, we should do what we can to correct their vision and hearing loss and stay aware of drugs that harm the brain and increase dementia risk, such as chronic high doses of anticholinergics. Note that none of these recommendations has harmful side effects.”