Healthy diets seem to neurodegenerative diseases like Alzheimer’s. But new research calls everything we thought we knew about the Mediterranean diet into question. Why is the link between diet and dementia so hard to prove?
The number of people living with dementia is projected to more than triple by 2050, soaring to 152 million cases worldwide. Not all types of dementia are preventable, but mounting evidence points to the possibility that some cases are. With certain environmental and lifestyle interventions, that “some” could be as substantial as two in five dementia cases delayed or dodged altogether. When it comes to a specific, clear set of instructions on How to Prevent Dementia, however, the research leaves much to be desired.
For example, there was much discussion following 2022’s Alzheimer’s Association International Conference about early data from a 60-year study looking at how highly processed foods may be expediting cognitive decline in older adults. On the flip side, some researchers are “certain” that good nutrition lowers one’s risk of future cognitive impairment and dementia. But despite decades of study there is still broad consensus that the links between brain function and foods or food groups are, as of yet, inconclusive. With so encouraging evidence, why is the idea of a “dementia prevention diet” so hard to prove?
Studying nutrition: It’s complicated
Earlier this year, a Nutrition for Dementia Prevention Working Group made up of 27 leading researchers in the Alzheimer’s and dementia field laid out recommendations to help solidify the science around the relationship between nutritional diets and lower dementia risk. The group’s guidelines were published in The Lancet Health Longevity, where the authors also highlight the limitations of existing research.
“Many trials have not found that making people eat healthy or exercise is translating into benefits in the ways that is expected from the epidemiological research,” said Dr. Hussein Yassine, associate professor of medicine and neurology at the Keck School of Medicine of USC, said. “That means either there is no causal connection, or that these studies have not been properly designed.”
The researchers involved in creating these guidelines spent two years looking at the vast body of evidence linking nutrition and dementia risk. The results of nutritional research, they found, are not always straightforward. For example, it is known that a Mediterranean-style diet is healthy and that study participants who adhere to this diet are less likely to develop Alzheimer’s or other forms of dementia. But is the diet itself the protector? Or are there other factors at work behind the scenes?
What if, for example, the consumption of a Mediterranean diet were linked to some other influential but unmeasured factor, such as socioeconomic status, which is also linked to brain health?
In addition to unmeasured variables, Yassine notes that studies may often be too short to spot any meaningful effects of a dietary intervention on cognition. “If it takes five to 10 years,” he said, “then studies that lasted for two years or less are not accurately reflecting the effect of the diet on cognition.”
Studies that have hung in there for an entire decade have still found a positive correlation between a healthy diet and a lower risk of Alzheimer’s and dementia. But the working group’s recommendations go beyond simply making studies longer.
So, what’s the deal with the Mediterranean diet and Alzheimer’s dementia risk?
In October 2022, one of the largest studies to date found no association between the Mediterranean diet and dementia risk, calling into question years of previous assumption — and data — that the diet has a protective effect.
The new study, conducted by researchers from Lund University in Sweden and published in Neurology, recruited 28,000 cognitively healthy people with an average age of 58, following them for a 20-year period to see how adherence to dietary recommendations affected brain health.
At the very start, participants filled out a seven-day food diary, a food-frequency questionnaire to detail how often they consumed different foods in the past year, and also completed an in-person interview with the researchers about their dietary habits. Using this information, the study also excluded people who had only recently changed their diet. Their results were negative.
Isabelle Glans, MD, who led the study pointed out that the data showing the effects of diet on dementia risk is still mixed.
“While our study does not rule out a possible association between diet and dementia,” Glans said, “we did not find a link in our study, which had a long follow-up period, included younger participants than some other studies and did not require people to remember what foods they had eaten regularly years before.”
After 20 years, around 7 percent of participants were diagnosed with dementia which included Alzheimer’s disease and vascular dementia. On average, the participants who were diagnosed with dementia were several years older at the start of the study. Taking into account age, gender, and education, the researchers did not find a link between conventional dietary recommendations in Sweden (which are similar to those in the U.S.) and a reduced risk of dementia or levels of beta-amyloid in cerebrospinal fluid.
The authors also noted limitations in their study: As with most to all observational lifestyle studies, there may be errors in the way some individuals self-reported their food intake. While diet is thought to stay stable throughout life, the researchers did not account for any potential changes over the 20 years. They also didn’t measure cognitive function in their participants, relying on diagnoses from a database which may lead to an undercounting of dementia cases. Finally, since all of the participants came from the city of Malmö, it is unclear whether these results are generalizable to other races, ethnicities or populations.
Nils Peters, a physician at the University of Basel in Switzerland who was not involved in the study wrote an editorial for Neurology about it: “Diet on its own may not have a strong enough effect on memory and thinking, but is likely one factor among others that influence the course of cognitive function,” Peters wrote. “Dietary strategies will still potentially be needed along with other measures to control risk factors.”
This is in line with other studies that found combining lifestyle, diet, and social interventions, may be effective in reducing the risk of developing dementia.
Think of Indiana Jones and Raiders of the Lost Ark. Remember when the titular protagonist attempts to steal a relic on a pressure plate — swapping it out for another heavy object to prevent the trap from triggering and sending a giant boulder after him? In the movie, he failed to stop the trap from triggering. But by combining multiple decoy objects together, he could have prevented the trap from going off. Perhaps, dementia can only be achieved by combining different types of interventions together — like exercise, diet, and social activities.
Using brain biomarkers and the mircobiome to analyze impact of a healthy diet
Yassine and the Nutrition for Dementia Prevention Working Group argue that leveraging biomarkers from brain imaging, blood tests and can provide valuable information about how food and nutrients are processed by the body and how they may impact the brain. According to Yassine, neglecting these biomarkers in participants is where some studies fall short. “You cannot fully study how the diet is working without studying the microbiome,” he said.
The researchers also suggested, in addition to the current gold-standard of large randomized controlled trials, using other types of trials too. Rather than only looking at broadly at a participant group of 100,000 people, the authors say, smaller personalized studies could help shed light on more nuanced factors, such as an individual’s genetic risk, diet and microbiome, and their relationship to brain health. The working group also argues that this preventative research concerned with diet and dementia risk should start in participants’ midlife years, before the symptoms of Alzheimer’s or dementia set in.
By measuring these biomarkers, collecting information about other risk factors, and carefully tracking diet and nutritional intake, it might be possible to finally answer how and why diet is protective for dementia. There might finally be a clear, conclusive answer as to which foods are most protective for individuals carrying a specific risk factor, or whether a person is getting enough of a specific vitamin or nutrient to maintain brain health.
The more trial design can improve, says Dr. Lon Schneider, professor of psychiatry and the behavioral sciences at the Keck School of Medicine, the better chance people have to prevent Alzheimer’s and dementia.
“It is important that future trials yield accurate results,” he said, “that can be translated into better clinical care for patients.