“Many trials have not found that making people eat healthily or exercise is translating into benefits in the ways that are expected from the epidemiological research,” said Hussein Yassine, MD, associate professor of medicine and neurology at the Keck School of Medicine of USC and the Kenneth and Bette Volk Chair of Neurology of USC. “That means either there is no causal connection or that these studies have not been properly designed.”
To understand this discrepancy between epidemiological research and clinical trials, Yassine led the Nutrition for Dementia Prevention Working Group, a team of scientists who spent two years surveying the existing literature on nutrition and dementia risk. Their analysis, just published in The Lancet Healthy Longevity, identifies significant limitations to current trials that impact 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).
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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 is hard to separate nutritional information from other factors that might also play a role, such as where a person lives, contemporary healthy lifestyles, or whether they have access to proper medical care.
Most of the clinical research on food and brain health may not have been conducted over some time long enough 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,” said Yassine, “then studies that lasted for two years or less are not accurately reflecting the effect of the 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, an accepted vitamin D level sustains bone health, but the same cannot be said for nutrients that impact cognitive health.
Embracing new technology and new areas of research
The group points out that utilizing 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 that target clinical outcomes.
Technology, such as brain imaging can be highly effective in tracking changes in the brain over time. Likewise, they point out 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 most potent genetic risk factor for late-onset Alzheimer’s disease. He 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 can also improve the outcomes of research. Yassine noted that people benefit from food differently based on differences in the microbiome. “You cannot fully study how the diet works without studying the microbiome,” said Yassine. There is also a need to 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 utilizing a wider variety of study designs, not just randomized controlled trials, and more thought should go into choosing participants in trials.
They note that one strategy would be to design small, personalized trials that consider participants’ genetic risk, quality of their diet, and analysis of their microbiome while utilizing biomarkers that reflect brain functions. Another approach involves designing large, pragmatic electronic health trials using mobile phones or tablets to collect data aimed at people with dementia risk factors.
While much of the research to date has focused on older people, several high-quality cohort studies suggest that middle life could be an optimal time to begin such research before the changes associated with dementia set in so that researchers can track changes over time. Additionally, the group points out that studies need to consider the dietary preferences of underrepresented groups, some of whom are disproportionately affected by dementia.
“This is an important document for anyone researching diet and how it relates to dementia,” said Lon Schneider, MD, Professor of Psychiatry and the Behavioral Sciences at the Keck School of Medicine and Della Martin Chair in Psychiatry and Neuroscience. Dr. Schneider also serves on The Lancet Commission on dementia prevention, intervention, and care. “It is important that future trials yield accurate results translated into better clinical care for patients.”
“We are pleased to contribute to this working group and help turn these recommendations into reality,” said Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of medical and scientific relations.
Source: Eurekalert
