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 higher or lower intake of certain foods and dementia risk. But clinical research trying to connect specific nutrients or diets with cognitive function has found no convincing evidence.
“Many trials have not found that getting people to eat healthy or exercise translates into benefits in the way that epidemiological research would hope,” said Hussein Yassine, MD, associate professor of medicine and neurology in the School of Medicine. Keck Professor of Medicine at USC and the Kenneth and Bette Volk Chair of Neurology at USC. “That means either there is no causal connection or these studies have not been properly designed.”
To understand this discrepancy between epidemiological research and clinical trials, Yassine led the Nutrition for Dementia Prevention Task Force, a team of scientists that spent two years reviewing the existing literature on nutrition and dementia risk. His analysis, recently published in Healthy Longevity Lancet, identifies the main limitations of existing trials affecting 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).
Nutrition 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 hard 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 health care.
Most of the clinical research on food and brain health may not have been conducted over a long enough period of time for the results to be meaningful because it’s unknown how long it takes a healthy diet to affect cognition . “If it takes five to 10 years,” Yassine said, “then studies that lasted two years or less don’t 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 thought to affect cognitive health.
Adopt new technologies and new areas of research.
The group notes that the use of biomarkers instead of cognitive tests, the most widely used tool to analyze the success of an intervention, can lead to more significant 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. They also 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 under study.
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 the diet works without studying the microbiome,” Yassine said. There is also a need for a greater understanding of the underlying relationship between the gut microbiota and cognition in large populations of diverse individuals.
A new approach
Ultimately, 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 trial participants.
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 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 doing research on 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 Endowed Chair in Psychiatry and Neuroscience. . Dr. Schneider is also a member of The Lancet Commission on Dementia Prevention, Intervention and Care. “It is important that future trials produce accurate results that can translate into better clinical care for patients.”
“We are pleased to contribute to this task force and help turn these recommendations into reality,” said Heather M. Snyder, Ph.D., vice president of medical and scientific relations for the Alzheimer’s Association.
Reference: Yassine HN, Samieri C, Livingston G, et al. Nutritional state of the science and dementia prevention: recommendations from the task force on nutrition for dementia prevention. Healthy Longevity Lancet. 2022;3(7):e501-e512. do: 10.1016/S2666-7568(22)00120-9
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