Age-related brain atrophy, the gradual loss of neurons and shrinkage of brain tissue, is a natural part of aging, which can lead to cognitive decline and other neurological issues. While so far aging cannot be prevented, recent research from an 18-month dietary intervention offers hope that lifestyle and dietary changes can slow brain aging. A new international study, led by Ben-Gurion University of the Negev as part of the DIRECT PLUS Brain MRI trial, has brought to light how blood sugar control can significantly impact brain health.

Brain age, as evaluated by MRI measurements of the hippocampus and lateral ventricles, reflects the biological aging of the brain, which can differ from a person's chronological age. Chronological age is the number of years lived, while brain age indicates the brain's actual health. Typically, as we age, the hippocampus shrinks and the lateral ventricles expand, serving as markers of brain aging. Some individuals have a brain age younger or older than their chronological age. A younger brain age suggests better cognitive health, while an older brain age may indicate accelerated aging and increased risk of cognitive decline.

The study, which was published recently in The American Journal of Clinical Nutrition 2024 https://www.sciencedirect.com/science/article/abs/pii/S0002916524007457 , was conducted by an international team of brain and nutrition experts, including researchers from Ben-Gurion University, Harvard University, Leipzig University, and more. The research was primarily carried out by Ph.D. student Dafna Pachter and overseen by Prof. Iris Shai, along with several international collaborators.

A previous study published two years ago (American Journal of Clinical Nutrition 2022 https://pubmed.ncbi.nlm.nih.gov/35021194/), reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 months.

In the current study, the researchers aimed to understand the mechanism by which the slowing of brain atrophy occurs.

The study found that a decline in HbA1c, and key markers of long-term blood sugar levels, are associated with significant positive changes in specific brain regions commonly affected by age-related atrophy. Brain MRI results showed that lower HbA1c levels corresponded to greater deviations in the thalamus, caudate nucleus, and cerebellum – areas crucial for cognitive function, motor control, and sensory processing. The study suggests that improved blood sugar control could be one of the most important factors in slowing down age-related brain changes.

The Green Mediterranean Diet shows promise

Earlier research has highlighted the benefits of the Green Mediterranean (Green-Med) diet, including better blood sugar control. The Green-Med diet is rich in polyphenols from plant-based sources like Mankai (a high-protein aquatic plant) and green tea, while being low in red and processed meats. The current study further strengthens this connection by suggesting that the Green-Med diet may not only support metabolic health but also exert protective effects on brain structure and function.

DIRECT PLUS trial – one of the largest brain MRI intervention studies in the world

The DIRECT PLUS trial, one of the longest and largest brain MRI studies conducted to date, involved approximately 300 participants who were divided into three dietary groups. Whole-brain MRI measurements were taken before and after the 18-month trial to track changes in brain health. The researchers used Hippocampal Occupancy (HOC), as a proxy for brain age which predicts future risk of dementia. HOC typically decreases with age. Interestingly, some participants exhibited a brain age either younger or older than their chronological age.

Using NeuroQuant, an FDA-authorized fully automated tool, the research team quantified and segmented the brain MRI-derived data. The study aimed to examine whether improved glycemic control and specific dietary components could slow down brain aging. The results indicated that participants who managed to improve their blood sugar levels and achieve normal glucose status experienced a more pronounced attenuation of brain aging. Notably, those who consumed higher amounts of green tea and Mankai duckweed shakes demonstrated the most significant improvements in both blood sugar levels and brain health.

Glycemic control and polyphenols: the key to a younger brain age?

The study’s lead researcher, Prof. Iris Shai, from Ben-Gurion University, an adjunct professor at Harvard University, and an Honorary Professor at Leipzig University, explains, “Maintaining low blood sugar levels, even within the normal range, shows promise for preserving a younger brain, especially when combined with a healthy diet and regular physical activity. Specifically, polyphenols found in plant-based foods may cross the blood-brain barrier and help reduce brain inflammation, which is crucial for memory”.

Dafna Pachter, a Ph.D. student and the first author of the paper, adds, "This trial offers a safe approach to potentially slow down our brain aging—by adopting the components of a green-Mediterranean diet."

A pathway to reducing age-related cognitive decline

This study is one of the first large-scale trials to directly link dietary changes, particularly those associated with the Green-Med diet, to improved glycemic control and slower brain aging. While further research is needed to fully understand the mechanisms at play, these results suggest a potential avenue for reducing the risk of age-related cognitive decline through relatively simple dietary adjustments.

The DIRECT PLUS trial was funded by grants from the German Research Foundation (DFG), Israel Ministry of Health, Israel Ministry of Science and Technology, and the California Walnuts Commission. None of the funding providers were involved in any stage of the design, conduct, or analysis of the study, nor did they have access to the study results before publication.