A Mindful Approach to MIND Diet Research

As a young researcher, Puja Agarwal, PhD, is chasing much more than the low-hanging fruit.

Agarwal, a nutritional epidemiologist and newly minted assistant professor of internal medicine at Rush University, uses population studies to explore how the consumption of particular food groups, including fruits like strawberries, and nutrients affect brain health over time.

Agarwal was first hired at Rush in 2016 as a postdoctoral research fellow to work with the late Martha Clare Morris, a developer of the highly regarded MIND diet, who died in February 2020. While Agarwal thinks her own deep, longtime interest in nutrition would have propelled her into her present field in any case, she says she was fortunate to have spent four years working with Morris at the nexus of nutrition and cognitive health.

“She was one of the great scientists in the field and a great mentor,” Agarwal says. “We miss her tremendously. To the best of our abilities, we will move forward with her research legacy.”

Berry picking

As part of Morris' team at Rush, Agarwal has looked deeper into elements of the MIND diet to show how certain foods may help prevent dementia and other age-related conditions. She has looked at the benefits for the brain of eating leafy green vegetables and, more recently, strawberries.

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“Berries are an important component of the MIND diet,” Agarwal says, but until recently blueberries got most of the attention due to their motor and cognitive health benefits.

Strawberries are coming into their own now, though. They are a great source of vitamin C and polyphenols, a bioactive category of plant compounds, many of which have well-established health benefits.

Agarwal and the Rush team found that of the 925 participants who were followed for nearly 20 years in the Rush Memory and Aging Project (MAP), those who ate strawberries more than once a week were 32% less likely to develop Alzheimer's dementia than those who didn't eat them. The participants’ ages ranged from 58 to 98 years old. They were dementia-free at the outset and received regular clinical evaluations over the years as part of the study.

Bioactive components in strawberries that may help reduce the incidence of Alzheimer’s disease, the most common cause of dementia among older adults, include anthocyanidins, especially pelargonidin. Agarwal is finishing up a different study now that is investigating pelargonidin, a pigment found naturally in strawberries, to see if it has an association with Alzheimer’s disease pathology in postmortem brains of MAP participants that strengthens the association of strawberries with lower incidence of Alzheimer's disease.

Questions about other berries have been added to research questionnaires for future Rush studies. “Our data is robust for strawberries. Going forward, we'll have more data on other berries,” she says.

Data mining

For most of the work Agarwal has done at Rush, she has used data from Rush’s MAP and Chicago Health and Aging Project (CHAP) databases, which collect information about the same populations over time to learn more about chronic diseases that affect cognition and motor function, including AD.

But using data to make observations “doesn’t really establish the cause and effect” relationship between diet and brain health, Agarwal says. “That's why Dr. Morris had this vision of doing a trial,” which is underway now, Agarwal says. More than 600 participants follow one of two diets, including the MIND diet, for three years at two sites, at Harvard University in Massachusetts and the Rush Oak Park Hospital campus in the western suburbs of Chicago.

“We're hoping for robust results by next year, when the trial will be over” that will show that the MIND diet really can protect the brain, says Agarwal, whose research appointment is in the Division of Digestive Diseases and Nutrition.

Recipe for success

Agarwal grew up in a small town in India, and went to college and got a master's degree at the University of Delhi. She came to the United States to study for her PhD in human nutrition at the University of Illinois at Chicago (UIC) and was an instructor at UIC before she came to Rush.

When she was starting her studies in India, some people who learned about the work she wanted to do were confused, and they concluded she must be talking about culinary school — that she was planning to be a chef. Things have changed since then, she says; more people understand now that what we eat can profoundly affect our health, and that understanding nutrition is not only scientific but also crucial to our being able to make appropriate food choices.

While she was still in India, Agarwal's late father was diagnosed with Parkinson's disease. He was in his late 50s at the time; his health declined rapidly. Agarwal says her mother wanted to know if there were foods he should be eating to slow the disease.

“Is there something a family can do?” Agarwal says. “We couldn't find any answers at that time.”

In 2018, she worked on a study that showed the MIND diet can reduce the incidence and progression of parkinsonian signs in older adults.

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Morris and her colleagues developed the MIND diet at Rush around 2015, and for years, it has been consistently ranked by U.S. News & World Report as one of the best diets for health. The MIND diet is a hybrid of two older regimens — the Mediterranean diet, developed in the 1960s, when scientists began to show that foods traditionally eaten in cultures around the Mediterranean Sea — fish, whole grains, olive oil, legumes, fruits and vegetables — could improve health. The other was the Dietary Approaches to Stop Hypertension (DASH) diet from the 1990s, which was tailored to lower blood pressure.

The MIND diet focuses on nutrients that promote brain health and head off cognitive decline. Instead of the two to three fish servings a week the Mediterranean diet calls for, the MIND diet advises people to eat just one. Research has shown that's enough for brain health, Agarwal says.

Even so, “it's hard to get people to eat these healthier foods if they haven't been raised with them,” Agarwal says. But if people can make the diet shift, data suggests they would benefit. Agarwal recently did a study showing that even partially eating a Western diet — heavy on red meat, animal fats, sweets and fried food — can cancel out the Mediterranean diet's benefits for slowing cognitive decline.

“That needs to go out as a public health message,” she says. “The impact of the good food diminishes when we eat more of the bad food.”

‘Good place for a new investigator’

One of the things Agarwal likes about working at Rush is the many multidisciplinary teams at work there, which results in plenty of opportunities for collaboration. For example, she works closely with the Rush Alzheimer’s Disease Center and has collaborated with some of Rush's orthopedics researchers on determining whether metals shed by joint implants could affect brain health.

“Rush is a really good place for a new investigator,” she says.

Agarwal has also received funding from the Michael J. Fox Foundation, which supports PD research. Philanthropic grants like that one are another great way for a young researcher like her to establish a research track record, she says.

Agarwal says that the importance of her work overwhelms her at times.

“Nutrition and diet play a role in pretty much every outcome in our lives, from gestation to old age — cancer, Alzheimer's disease, diabetes, other diseases,” she says. “They are part of our overall well-being.”