Summary Observational studies suggest that nutritional factors have potential cognitive benefit. However, systematic reviews of randomized trials of dietary and nutritional supplements have largely reported null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal Opinion, the Dementia Prevention Nutrition Working Group presents what they consider limitations in existing nutrition clinical trials for dementia prevention. Based on this evidence, we propose recommendations for incorporating dietary patterns and the use of genetic and nutritional assessment tools, biomarkers, and novel clinical trial designs to guide future trial development. Nutrition-based research has unique challenges that may require testing more tailored interventions in specific risk subgroups, identified by nutritional and other biomarkers, and pragmatic, large-scale study designs for more generalizable public health interventions across diverse populations. After two years of analysis, the Dementia Prevention Nutrition Working Group makes recommendations to improve nutrition clinical trials in the future. |
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Anyone searching the Internet for brain-healthy foods will find no shortage of stories with dietary recommendations. Some of those stories point to observational studies that have suggested a link between eating more or less of certain foods and the risk of dementia. But clinical research attempting to connect specific nutrients or diets to cognitive function has found no convincing evidence.
"Many trials have not found that getting people to eat healthily or exercise translates into benefits in the way that is expected from epidemiological research," said Hussein Yassine, MD, associate professor of medicine and neurology at the School of Medicine. of Medicine at USC and the Kenneth and Bette Volk Chair in Neurology at USC. “That means there is no causal connection or these studies have not been designed properly.”
To understand this discrepancy between epidemiological research and clinical trials, Yassine led the Dementia Prevention Nutrition Working Group, a team of scientists who spent two years examining the existing literature on nutrition and dementia risk. Their analysis, just published in The Lancet Healthy Longevity , identifies the main limitations of existing trials that affect how nutrition affects the brain and offers a set of recommendations to guide and improve future research. This work was supported by a grant from the National Institutes of Health (NIH).
Nutritional research presents unique challenges
Yassine points out that nutrition research in general is difficult to execute well. Epidemiological studies show, for example, an association between people who eat fatty seafood, such as salmon, and a lower incidence of dementia. But it’s difficult to separate nutritional information from other factors that could also play a role, such as where a person lives, concurrent healthy lifestyles, or whether they have access to appropriate medical care.
Most clinical research on food and brain health may not have been done over a long enough period of time for the results to be meaningful because it is unknown how long it takes for a healthy diet to affect cognition. "If it takes five to 10 years," Yassine said, "then studies that lasted two years or less do not accurately reflect the effect of diet on cognition."
Future research will also improve if more research is done to understand how much of a specific nutrient a person needs to achieve optimal brain health. For example, there is an accepted level of vitamin D that maintains bone health, but the same cannot be said for nutrients that are thought to affect cognitive health.
Adopt new technologies and new areas of research.
The group notes that using biomarkers instead of cognitive testing, the most widely used tool to analyze the success of an intervention, can lead to more meaningful immediate results that can guide longer interventions aimed at clinical outcomes. Technology, such as brain imaging , can be extremely effective at tracking changes in the brain over time.
Additionally, they note that testing blood or stool samples for certain biomarkers, such as suboptimal intake of a specific nutrient, can also be used to select the best participants and help determine whether study participants are responding to the intervention being studied.
Genetic testing can also be an effective tool, according to Yassine, who studies apolipoprotein E4, or APOE4, which is the strongest genetic risk factor for late-onset Alzheimer’s disease. She noted that people with this genetic variant respond differently to diet than non-carriers. Here, genetic testing can improve the quality of research with more personalized interventions.
Emerging knowledge about the microbiome may also improve research results. Yassine noted that people benefit from foods differently based on differences in the microbiome. “You can’t fully study how diet works without studying the microbiome,” Yassine said. There is also a need for greater understanding of the underlying relationship between gut microbiota and cognition in large populations of diverse individuals.
A new approach
Finally, the group concluded that researchers should consider using a wider variety of study designs, not just randomized controlled trials, and that more thought should be given to choosing participants in trials.
They note that one strategy would be to design small, personalized trials that consider participants’ genetic risk, the quality of their diet, and analysis of their microbiome while using biomarkers that reflect brain functions. Another approach is to design large pragmatic electronic health trials using mobile phones or tablets to collect data, targeting people with risk factors for dementia.
While much of the research to date has focused on older people , several high-quality cohort studies suggest that midlife may be an optimal time to begin such research, before the changes associated with aging occur. dementia, so researchers can track changes over time. Additionally, the group notes that studies should consider the dietary preferences of underrepresented groups, some of whom are disproportionately affected by dementia.
This is an important paper for anyone researching diet and how it relates to dementia," said Lon Schneider, MD, professor of psychiatry and behavioral sciences at the Keck School of Medicine and Della Martin Chair in Psychiatry and Neuroscience. Dr. Schneider is also part of The Lancet Commission on Dementia Prevention, Intervention and Care. “It is important that future trials produce accurate results that can be translated into better clinical care for patients.”
"We are pleased to contribute to this task force and help make these recommendations a reality," said Heather M. Snyder, Ph.D., vice president of medical and scientific relations for the Alzheimer’s Association.
This Personal Viewpoint was supported by funding from the National Institute on Aging (NIA R13AG069386) and the Alzheimer’s Association.
