Cognition Improves After Supplemented Mediterranean Diet, Finds a Rare Trial

Cognition improves in older people who eat a plant-based Mediterranean diet with antioxidant-rich extra virgin olive oil or mixed nuts, according to rare clinical trial research published by JAMA Internal Medicine.

“This is a significant pioneering study,” Nikolaos Scarmeas, M.D., M.Sc., Ph.D., told Bioscience Technology. Scarmeas, a Columbia University Associate Professor of Neurology, was not involved with the work. “There are a lot of observational studies suggesting association between a Mediterranean-type diet and a series of medical conditions and diseases. But there are few experimental interventional studies, i.e. clinical trials, securing and providing high level of evidence for such an association. This is in particular for neurological diseases. The parent study of the current one, the PREDIMED, very convincingly demonstrated a protection of a Mediterranean-type diet particularly for stroke. This small sub-study suggests a protective effect for cognitive decline too.”

Said senior author Emilio Ros, M.D., Ph.D., of the Institut d'Investigacions Biomediques August Pi Sunyer, Hospital Clinic, Barcelona: “The major surprise was the great power of foods and dietary patterns to beneficially influence health.”

Cognition and diet, past and present

It has long been believed that oxidative stress plays a major role in cognitive decay. Prior research links Mediterranean diets with cognitive function and a lower risk of dementia. But observational research looking at this had limitations. “Gold standard” research in this area of science is clinical trial research

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Ros’ randomized clinical trial enrolled 447 cognitively healthy volunteers, of whom 223 were women. The average age was almost 67 years old. All were at high cardiovascular risk—without having cardiovascular disease- and enrolled in the Prevencion con Dieta Mediterranea nutrition intervention.

The breakdown was as follows: 155 people were told to eat a Mediterranean diet in addition to one liter of extra virgin olive oil per week; 147 were told to eat a Mediterranean diet with 30 grams per day of a mix of walnuts, hazelnuts and almonds; 145 individuals were told to follow a low-fat control diet.

Cognitive change over time was measured with a slew of neuropsychological tests. The tests looked at memory, frontal (attention and executive function), and global cognition. Follow-up tests were available on 334 participants after an intervention that lasted a median of four years.

At the conclusion of the follow-up, there were 37 cases of mild cognitive impairment. Seventeen of those (13.4 percent) occurred in the Mediterranean diet plus olive oil group; eight (7.1 percent) occurred in the Mediterranean diet plus nuts group; and 12 (12.6 percent) occurred in the low-fat control group. There was no dementia in patients completing the follow-up.

People in the low-fat control diet experienced a significant decrease from baseline in all studied areas of cognitive function. By comparison with that control group, memory improved significantly in the Mediterranean diet plus nuts, while frontal and global cognition improved in the Mediterranean diet plus olive oil group. Ros’ team found that changes in the two Mediterranean diet arms were more like each other than when comparing the individual Mediterranean diet groups with the low-fat diet control group.

The overall PREDIMED trial

“The PREDIMED trial, of which the present work is a sub study, has already revealed that Mediterranean diets supplemented with extra-virgin olive oil, or mixed nuts, reduce cardiovascular diseases, diabetes, hypertension, atrial fibrillation, depression, and so on, by comparison with a control diet, based on advice to reduce dietary fat,” Ros told Bioscience Technology. “Now we show that these healthy Mediterranean diets, enriched with high antioxidant foods, also counteract age-related cognitive decline, as assessed by a battery of neuropsychological tests administered to older, but cognitively healthy, participants at entry and at the end of the study, a mean of 4.1 years later.”

Ros’ team launched the trial because they knew that “like development of all chronic degenerative diseases, declining brain function is part of aging and is believed to be mediated by oxidative stress,” Ros said. “We hypothesized that long-term adherence to a healthy, antioxidant-rich diet would enhance brain function and contribute to healthy aging.”

Next up

Scarmeas was not surprised at the study’s outcome, “given the observational epidemiological evidence. This paper confirms previous findings.” Furthermore, he said: “There should definitely be more clinical trial attempts to confirm, validate and explore in a more detailed way these findings, i.e. the relation between a Mediterranean-type diet and Alzheimer’s disease / cognitive aging. These clinical trials should have cognition as the primary target-outcome, and should be better designed so that questions related to limitations of the current study are addressed.”

Nevertheless, Scarmeas said: “It is always reassuring to see a clinical trial providing evidence along the same lines as observational studies.”

Agreed Ros: “The obvious next step is to examine the effect of the PREDIMED diets on the incidence of neurodegenerative diseases, including Alzheimer’s, as this was a pre-specified secondary outcome of the trial. We are into it. We are also involved in a large trial assessing the effect of a diet enriched with walnuts versus a control diet on cognition and MRI-assessed brain structure and function. Any other randomized clinical trials of dietary patterns or foods for effects on cognition would be welcome.”

Example of cognitive improvement

An example of improvement seen after a supplemented Mediterranean diet, Ros told Bioscience Technology, occurred with the Trail Making Test, which is “a measure of sustained attention, an executive function, in which a sheet of paper with the numbers one to 25 written at random inside small circles is presented to the examinee. Using a pencil or ballpoint, the test taker has to unite the numbers consecutively with straight lines, beginning with 1, then 2, then 3, until 25. The time it takes to complete the task is computed. One improvement in this test was that, at baseline it took 58 seconds to complete the task. At the end of the study, it took 47 seconds.”