BGU (Israel) and Harvard, Leipzig, Tulane : lower accumulation of abdominal fat is associated with a significant slowing of brain atrophy

A groundbreaking long-term MRI study demonstrates that lower accumulation of abdominal fat (visceral fat), measured throughout the entire follow-up period, is associated with a significant slowing of brain atrophy, preservation of key brain structures, and better cognitive performance in late midlife – independent of weight loss. The findings suggest that the relationship between abdominal fat and brain aging is likely mediated primarily through glucose control and insulin sensitivity. The study is the first to link repeated MRI-based measurements of cumulative visceral fat with long-term trajectories of brain aging and cognition. The study is based on advanced MRI imaging of the brain and abdomen and includes 533 women and men in late midlife who were followed for 5 to 16 years after participating in four large, long-term, controlled dietary clinical trials: DIRECT, CASCADE, CENTRAL, and DIRECT-PLUS, led by Prof. Iris Shai of Ben-Gurion University of the Negev, Dean of the School of Sustainability at Reichman University, and an adjunct Professor at Harvard University. During follow-up, repeated MRI measurements of visceral fat and brain structures were conducted, along with cognitive assessment using the MoCA test.

The findings show that lower accumulation of visceral fat over the years was associated with higher MoCA scores, as well as preservation of total brain volume, gray matter volume, and the Hippocampal Occupancy Score – a sensitive marker of brain aging and memory. In parallel, a slowing in the expansion of the brain ventricles was observed, a process that constitutes a well-established marker of brain atrophy.

Prof. Iris Shai: “The findings point to glucose control and reduction of visceral abdominal fat as measurable, modifiable, and achievable targets in midlife – with real potential to slow brain degeneration and reduce the risk of cognitive decline.”

The study was conducted at Ben-Gurion University of the Negev in collaboration with researchers from Harvard University, Leipzig University, and Tulane University.

A unique longitudinal follow-up, which included three brain MRI scans over five years in a subgroup of participants, showed that persistently elevated levels of visceral fat over time were associated with a faster rate of brain volume loss, particularly in the hippocampus, and with accelerated enlargement of the brain ventricles. These associations were not observed for subcutaneous fat, either superficial or deep, nor for body mass index (BMI), highlighting the biological specificity of visceral fat. Moreover, the study found that reductions in visceral fat during an 18-month dietary intervention predicted better preservation of brain structures 5 and 10 years later, even after adjustment for weight loss and other factors. In other words, the reduction in abdominal fat itself – rather than weight loss per se – was the factor predicting long-term brain outcomes.

The study indicates that the association between visceral fat and brain aging is mediated primarily through glycemic balance. Fasting glucose and HbA1c levels were the only markers that predicted the rate of structural brain change over time, whereas blood lipid markers or inflammatory markers did not show a similar association. These findings support the hypothesis that insulin resistance and chronic dysregulation of glucose metabolism impair cerebral perfusion, compromise blood–brain barrier integrity and accelerate degeneration of gray matter and the hippocampus.

Dr. Dafna Pachter, the study’s first author, said: “Weight alone is not a sensitive marker of the profound metabolic changes occurring in the body. We found that even when weight loss is modest, sustained reductions in visceral fat – as measured across the entire period – are associated with preservation of brain structure and a slower rate of atrophy.”

Breakthrough Brain Study

This is the largest and longest study to date linking cumulative exposure to visceral fat and brain measures, assessed longitudinally using MRI, with the rate of brain aging and cognitive function. The integration of repeated measurements of abdominal fat, brain structures, and cognition makes it possible, for the first time, to identify a specific metabolic target – rather than general obesity – as a modifiable brain risk factor.

The study’s findings were published in Nature Communications

This study was funded by grants from the German Research Foundation (DFG; LeiCeM, center of Excellence) and the ERA-4-Health initiative.

Authors : Dafna Pachter#1, Hadar Klein#1, Omer Kamer1, Dana Tamar Goldberg Toren1, Liav Alufer1, Noa Ebstein Karamani1, Tomer Atlas1, Amit Yaary1, Idan Hagbi1, Yoash Chassidim2, Ilan Shelef3, Moti Salti4, Frauke Beyer5, Veronica Witte5, Assaf Rudich6, Uri Yoel3,7, Gal Ben-Arie3, Anat Yaskolka Meir1, Alon Kaplan1, Gal Tsaban1, Hila Zelicha1, Carmi Bartal8, Lu Qi9,10, Matthias Blüher11, Michael Stumvoll12, Uta Ceglarek13, Berend Isermann13, Dong D. Wang10, Meir J Stampfer10, Frank B Hu10, Galia Avidan4,14, Iris Shai*1,10,12,15

* Corresponding author: Iris Shai
1 The Health and Nutrition Innovative International Research Center, Department of Epidemiology, Biostatistics and Community Health Sciences, Faculty of Health
Sciences, School of Public Health, Ben-Gurion University of the Negev, Beer-Sheva, Israel
2 Department of Engineering, Sapir Academic College, Shaar Hanegev, Israel
3 Soroka University Medical Center, Beer-Sheva, Israel
4 Department of Psychology, Ben-Gurion University of the Negev, Beer-Sheva
Israel
5 Department of Neurology, Max-Planck-Institute for Human Cognitive and Brain
Sciences, and Cognitive Neurology, University of Leipzig Medical Center,
Leipzig Germany
6 Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences,
Ben-Gurion University of the Negev, Beer-Sheva, Israel
7 Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
8 Briuta Care Medical Center, Beer-Sheva, Israel
9 Department of Epidemiology, School of Public Health and Tropical Medicine,
Tulane University, New Orleans, Louisiana, USA
10 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA,
USA
11 Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the
Helmholtz Zentrum München at the University of Leipzig and University Hospital
Leipzig, Leipzig, Germany
12 Department of Medicine, University of Leipzig, Germany
13 University of Leipzig Medical Center, Institute of Laboratory Medicine, Leipzig,
Germany
14 Department of Cognitive and Brain Sciences and The School of Brain Sciences and
Cognition, Ben-Gurion University of the Negev, Beer-Sheva, Israel
15 School of Sustainability, Reichman University, Herzliya