A unique randomized trial is measuring the impact of diet on brain function on 600 older Americans

When I was younger, my mother often referred to the Friday fish fry as brain food, primarily to get me and my brother to clean our plates. I’ve since fallen in love with seafood and freshwater fish, but does it really help us our mental fitness? What about broccoli, beets, avocados, dark chocolate or other ‘smart’ choices listed on many dietary websites.

These are, actually, important questions to consider as the number of people with Alzheimer’s or other forms of dementia grows while promising drug candidates falter in the clinic. Alzheimer’s Disease International, an umbrella organization of more than 80 Alzheimer’s associations, says that the 46.8 million people estimated to be living with dementia in 2015 will be 131.5 million by 2050.

Stemming the tide of this horrible disease remains squarely focused on finding therapeutic solutions, where the overall success rate is around 4%, yet there has never been a randomized trial testing the impact of diet on brain function in older people.

Nutritional epidemiologist Martha Clare Morris, a ScD scientist at Rush University Medical Center in Chicago, is working to change that. Rush and Harvard University launched a study in February looking at the effects of diet on the decline of cognitive abilities among a large group of individuals 65 to 84 years who currently do not have cognitive impairment. The US National Institute on Aging is funding the US$20 million trial.

To be eligible to join, participants must have a family history of dementia, have a body mass index of at least 25, and follow a suboptimal diet. (More on that later). They can’t be cognitively impaired, or be a heavy user of alcohol.

The study is relying on the MIND diet—short for Mediterranean-DASH Intervention for Neurodegenerative Delay—which Morris developed several years ago based on numerous studies about what foods and nutrients have good effects on the functioning of the brain over time.

A clear-cut winner might be polyunsaturated fatty acids (PUFAs)—the so-called good fats found in seafood (salmon, tuna, sardines, shellfish) that appears to have had beneficial effects on a wide range of illnesses, from asthma to schizophrenia. On the other hand, exposure to foods that contain nitrates (bacon, cured meats), suspected of contributing to Alzheimer’s disease, would not be a good choice.

The MIND Study, which Dr. Morris leads, in collaboration with Dr. Frank Sacks, MD, a Professor in the Nutrition Department ofthe Harvard T.H. Chan School of Public Health and Dr. Vince Carey, of Brigham and Womens’ Hospital at Harvard University, is enrolling 600 older Americans who are overweight, eat poorly and have a history of Alzheimer’s disease or dementia.

Eureka Editor Regina McEnery spoke recently with Dr. Morris about the trial. Here is an edited transcript of their discussion.

RM: What exactly does a nutritional epidemiologist do?

MM: I look at nutrition and how it relates to disease and the development of disease in large populations. The first epidemiologists were in the area of epidemics but the field has really developed to study chronic diseases as well as many other things besides epidemics.

RM: How did you come to partner with Harvard?

MM: I got my doctorate degree in epidemiology at the Harvard School of Public Health and maintained relationships with my professors and colleagues there. One of my mentors at Harvard, Frank Sacks, spent his career doing diet intervention trials so I asked if he would collaborate on designing a trial that looked at nutrition and dementia.

RM: Why hasn’t a study like this been done before?

MM: For a number of reasons. The field of neurology and dementia has, in theory, been reluctant to think nutrition has anything to do with the brain. Part of that is that they aren’t trained in nutrition. The field has been slow to do the scientific studies to connect what foods and nutrients are important for the brain. Also, there is the huge problem of having the expertise to successfully get people to change their diet. That has been completely absent in the field of dementia.

RM: So if you prove the MIND diet impacts cognitive function, could you make a case that it might also help people already cognitively impaired?

MM: Well, the issue of whether consuming these foods when you have the disease could help slow cognitive decline is a totally different question. Our study is focused on prevention. Other trials would have to be done in people with mild cognitive impairment to see if it delayed progression and improved their quality of life.

RM: Can you talk a little bit about the design of the study?

MM: Half of the people will be counseled to adhere to the MIND diet and to reduce their calorie intake by 250 calories per day. The other group we are just focusing on calorie restriction. We will be doing extensive cognitive testing over the three-year period of the study to see if the MIND diet slows any kind of cognitive decline. We will also be doing brain MRIs and looking to see if the MIND diet decreases the amount of atrophy that occurs in older people, especially in the regions of the brain that are pertinent to Alzheimer’s disease.

RM: To qualify for this study you need to be on a suboptimal diet. How are you defining suboptimal?

MM: We are giving them a questionnaire and scoring their responses. We’ll be asking, for example, how often they eat fish…or potato chips.

RM: How will you determine if the trial participants are sticking to their diets?

MM: Everyone in the study is being assigned a case manager, who will meet with them weekly. They will also have to keep track of what they are eating. Periodically, we will have an independent person call them for a detailed interview about their diet or ask them to complete a diet questionnaire. Finally, we will be measuring their weight, and analyzing their blood for a long list of nutrients and dietary components.

RM: What have we learned from animal models about healthy eating and cognitive function?

MM: Most of the animal model studies that have been done have been nutrient focused. There have been a lot of animal models of Vitamin E showing it improves memory and decreases amyloid deposition, oxidative stress and inflammation. There is also a long list of studies on DHA found in fish oil showing it improves synaptic transmission and decreases oxidative stress. Comparatively, there are fewer animal models of Vitamin B, polyphenols and flavonoids.

RM: What’s been the reaction to this study among neurologists and other specialists?

MM: I get approached a lot from clinicians whose patients and their families are desperate for information. The Cadillac of scientific evidence has been the randomized trial and so there is a great deal of attention and expectations on this trial. Also, there has been a shift in attitudes over the last year or two toward nutrition and disease prevention. That is due to two European trials. One is the PREDIMED study of the Mediterranean diet and cardiovascular disease prevention. This trial included a small sub-study of 500 people that measured cognition at the end of 7 years and found better cognitive scores. Then there was a Finnish trial, called FINGER, that used a multi-model approach to slowing cognitive decline. One of the components of the intervention was diet consultations to get people to improve their diet. That was also positive. Given that our success rate for drug trials in Alzheimer’s and dementia is less than one percent, the reaction [to PREDMED and FINGER] was wow, maybe we need to take another look and change our attitude toward nutrition and other lifestyle interventions.