A 16-year-long study has found that lower cumulative visceral fat, rather than just weight loss, is independently associated with preserved brain volume, hippocampal integrity and higher cognitive scores in late midlife, with glucose control and insulin sensitivity identified as the primary mediating factors.
The study, published in Nature Communications, is the first to link repeated MRI-based measurements of cumulative visceral fat with long-term trajectories of brain ageing and cognition.
The research, led by Prof. Iris Shai of Ben-Gurion University of the Negev, Dean of the School of Sustainability at Reichman University, is based on advanced MRI imaging of the brain and abdomen and includes 533 women and men in late midlife who were followed for five to sixteen years after participating in following four large, long-term, controlled dietary clinical trials: DIRECT, CASCADE, CENTRAL and DIRECT-PLUS.
During follow-up, the scientists repeated MRI measurements of visceral fat and brain structures, along with cognitive assessment using the MoCA test.
The findings show that lower accumulation of visceral fat with time was associated with higher MoCA scores, as well as preservation of total brain volume, grey matter volume and the Hippocampal Occupancy Score (a marker of brain ageing and memory).
At the same time, a slowing of brain ventricular expansion was observed — a well-established marker of brain atrophy.
Prof. Iris Shai said: "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 longitudinal follow-up study with three MRI scans during a five-year period found that persistently high levels of visceral fat were linked to a faster rate of brain volume loss (particularly in the hippocampus) and increased enlargement of brain ventricles.
This association was not seen with subcutaneous fat or BMI, highlighting the specific impact of visceral fat.
Additionally, reductions in visceral fat during an 18-month dietary intervention predicted better preservation of brain structures five and ten years later, emphasising that decreasing abdominal fat — rather than overall weight loss — was crucial for long-term brain health.
The study suggests that the link between visceral fat and brain ageing is mainly influenced by glycaemic balance, as only fasting glucose and HbA1c levels predicted structural brain changes with time.
Insulin resistance and glucose metabolism disturbances may impair blood flow to the brain and accelerate the degeneration of grey matter and the hippocampus.
Dr Dafna Pachter, the study's first author, added: "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.
The integration of repeated measurements of abdominal fat, brain structures and cognition enables the identification of a specific metabolic target as a modifiable brain risk factor beyond general obesity.