Anyone searching the internet for brain-healthy foods will find no shortage of diet advice stories. Some of these stories point to observational studies that suggest a link between lower or higher intake of certain foods and dementia risk. But clinical studies trying to link specific nutrients or diets to cognitive function have not found conclusive evidence.
“Many trials have not found that getting people to eat healthily or exercise translates into benefits in the ways expected from epidemiologic studies,” said Hussain Yassin, MD, associate professor of medicine and neurology at the Keck School of Medicine. of USC and the Kenneth and Beth Volk Department of Neurology at USC. “This means that either there is no causal relationship or that these studies were not properly designed.”
To understand this discrepancy between epidemiologic research and clinical trials, Yassin led the Dementia Prevention Nutrition Task Force, 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 research 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).
Nutrition research presents unique challenges
Yassin points out that nutrition research in general is difficult to do well. Epidemiological studies have shown, for example, a link between people who eat fatty seafood, such as salmon, and a lower incidence of dementia. But it is difficult to separate nutritional information from other factors that may also play a role, such as where a person lives, accompanying healthy lifestyles, or whether they have access to appropriate medical 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 is not known how long it takes for a healthy diet to affect cognitive abilities. “If it takes five to 10 years,” Yassin said, “then studies lasting two years or less don’t accurately reflect the effect of diet on cognitive ability.”
Future research will also improve if more research is done to understand how much of a particular nutrient a person needs to achieve optimal brain health. For example, there is an accepted level of vitamin D that supports bone health, but the same cannot be said for nutrients thought to influence cognitive health.
Embracing new technologies and new areas of research
The group points out that using biomarkers rather than cognitive tests, the most commonly used tool to analyze the success of an intervention, may lead to more meaningful immediate results that can guide longer interventions targeting clinical outcomes. Technologies such as brain imaging can be extremely effective in tracking changes in the brain over time. Similarly, they point out that testing blood or stool samples for certain biomarkers, such as suboptimal intake of a specific nutrient, can also be used both to select the best participants and to determine whether study participants meet the intervention studied.
Genetic testing can also be an effective tool, according to Yasin, who studies apolipoprotein E4, or APOE4, which is the strongest genetic risk factor for late-onset Alzheimer’s disease. He noted that people with this genetic variant respond differently to diet compared to non-carriers. Here, genetic testing can improve the quality of research with more personalized interventions.
Emerging knowledge about the microbiome may also improve research outcomes. Yassin noted that people benefit from food differently based on differences in the microbiome. “You can’t fully study how diet works without studying the microbiome,” Yasin said. There is also a need to better understand the underlying relationship between gut microbiota and cognition in large populations of diverse individuals.
A fresh approach
Finally, the group concluded that researchers should consider using a wider variety of study designs, not just randomized controlled trials, and more thought should be given to the selection of trial participants.
They note that one strategy would be to design small, personalized trials that take into account participants’ genetic risk, the quality of their diet and analysis of their microbiome, while using biomarkers that reflect brain function. Another approach involves designing large, pragmatic e-health surveys using mobile phones or tablets to collect data targeting people with risk factors for dementia.
Although much of the research to date has focused on older adults, several high-quality cohort studies suggest that midlife may be the optimal time to begin such research, before dementia-related changes occur so that researchers can track changes over time. The group also states that studies should take into account 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 the Della Martin Chair in Psychiatry and Neurology. Dr Schneider also serves on the Lancet Committee on Dementia Prevention, Intervention and Care. “It is important that future trials provide 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, MD, Alzheimer’s Association vice president of medical and scientific affairs.
Reference: Yassine HN, Samieri C, Livingston G, et al. State of the science of nutrition and dementia prevention: recommendations of the Nutrition for Dementia Prevention Task Force. The Lancet Healthy Longevity. 2022;3(7):e501-e512. doi: 10.1016/S2666-7568(22)00120-9
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