Study design and workflow. The Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) study investigated the effect of successful weight loss after 18 months of lifestyle intervention on adiposity, cardiometabolic and brain health in all intervention groups. (a) Participants in the functional connectivity substudy (N=132) completed baseline measurements at T0. They were randomly assigned to three intervention groups: healthy diet guidelines (HDG), an active control group, Mediterranean diet (MED), and green-MED. All groups were combined with physical activity (PA). Eighteen months after the start of the intervention, all measurements were performed again (T18). (B) Measurements include anthropometric measurements, blood biomarkers, fat deposition, and structural and functional brain imaging. (C) Functional brain imaging was performed while subjects were at rest and used to estimate resting state functional connectivity (RSFC). RSFC measures the correlation between the time series of pairs of brain regions. (D) We fitted a linear support vector regression to predict chronological age from all pairwise correlations. We fitted the model to the Nathan Kline Institute (NKI) dataset, tested it and applied it to the Cambridge Center for Aging and Neuroscience (Cam-CAN) and the DIRECT-PLUS data. (e, left scatter plot) Based on the T0 data, we first calculated the expected aging trajectory as the linear relationship between the chronological and predicted age of all subjects. The fitted line represents the increase in predicted age relative to chronological age in the absence of an intervention. (e, right scatter plot) The fitted line was used to estimate the expected brain age at T18, given each participant’s T0 brain age and the time elapsed between the T0 and T18 magnetic resonance imaging (MRI) scans. We calculated the observed brain age by applying the brain age model to the T18 scans. The brain age attenuation was calculated as the expected brain age minus that observed at T18. Credit: eLife (2023). DOI: 10.7554/eLife.83604
Switching to a green Mediterranean diet has a positive impact on brain health, according to new research from Ben-Gurion University of the Negev. Weight loss reduced brain aging in a substudy of the DIRECT-PLUS trial.
DIRECT PLUS was a large-scale, long-term, 18-month clinical study with 300 participants. The sub-study was conducted by Prof. Galia Avidan from the Department of Psychology and Dr. Gidon Levakov, a former PhD student at the Department of Cognitive and Brain Sciences. Their findings were recently published in eLife.
The larger study was led by Prof. Iris Shai of Ben-Gurion University of the Negev, an adjunct professor of the Harvard School of Public Health and an honorary professor at the University of Leipzig, Germany, along with her former graduate student Dr. . Alon Kaplan and colleagues from Harvard and Leipzig Universities.
Obesity is associated with faster brain aging than would normally be expected. Researchers can capture this process by calculating a person’s “brain age” — how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to examine how certain factors, such as lifestyle, can influence brain aging on relatively short time scales.
Levakov, Kaplan, Shai and Avidan studied 102 individuals who met the criteria for obesity. At the beginning and end of the program, participants received a brain scan; at these times, more tests and measurements were also performed to capture other biological processes affected by obesity, such as liver health.
They used the brain scans taken at the beginning and end of the study to examine the impact of the lifestyle intervention on the aging process. The results showed that a 1% reduction in body weight resulted in the participants’ brain age being almost 9 months younger than the expected brain age at 18 months.
This attenuated aging was accompanied by changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes have previously been shown to negatively affect brain health in Alzheimer’s disease.
“Our study highlights the importance of a healthy lifestyle, including lower consumption of processed foods, sweets and beverages, for maintaining brain health,” said Dr. Levakov.
“We were encouraged to find that even a 1% weight loss was enough to impact brain health and lead to a 9-month reduction in brain age,” says Prof. Avidan.
The findings show that lifestyle interventions that promote weight loss may have a beneficial effect on the brain aging process seen in obesity. The next steps include finding out whether slowing obesity-induced brain aging leads to better clinical outcomes for patients. In addition, the study shows a possible strategy to evaluate the success of lifestyle changes on brain health.
As obesity rates rise worldwide, identifying interventions that positively impact brain health could have important clinical, educational, and social implications.
The research team of the DIRECT-PLUS trial was the first to introduce the concept of the green Mediterranean diet high in polyphenols. This modified Mediterranean diet is distinct from the traditional Mediterranean diet because of its more abundant dietary polyphenols (phytochemicals, secondary metabolites of plant compounds that provide various health benefits) and less red/processed meat.
In addition to a daily intake of walnuts (28 grams), the Green-Mediterranean dieters consumed 3-4 cups of green tea and 1 cup of Wolffia globosa (Mankai) plant green shake from duckweed per day for 18 months. The green water plant Mankai contains a lot of bioavailable iron, B12, 200 types of polyphenols and proteins and is therefore a good meat substitute.
More information:
Gidon Levakov et al, Assessed the effect of weight loss after 18 months of lifestyle intervention on brain age with functional connectivity at rest, eLife (2023). DOI: 10.7554/eLife.83604
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