Abdominal fat tied to reduced brain function in middle-aged men at high dementia risk

Higher abdominal fat, particularly around the pancreas, appears to contribute to lower cognition and brain volumes among middle-aged men at high risk of Alzheimer’s dementia, reports a study. This suggests a possible sex-specific link between distinct abdominal fat and brain health.

“[O]ur study provides new evidence pointing to the contribution of distinct fat depots to brain ageing and suggests that global obesity measures such as body mass index (BMI) may fail to identify important links in the fat–brain–cognition pathway,” said lead author Sapir Golan Shekhtman from The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel HaShomer, Israel.

Overall, 204 healthy middle-aged offspring of Alzheimer’s dementia patients (mean age, 59.44 years; female, 60 percent) were included in the study. They underwent abdominal magnetic resonance imaging to measure hepatic, pancreatic, visceral, and subcutaneous adipose tissue, as well as to assess cognition and brain volumes.

Higher hepatic fat percentage was found to correlate with reduced total gray matter volume (β, ‒0.17; p<0.01). Specifically, higher pancreatic fat in males showed an association with lower global cognition (males: β, ‒0.27; p=0.03; females: β, 0.01; p=0.93), executive function (males: β, ‒0.27; p=0.03; females: β, 0.02; p=0.87), episodic memory (males: β, ‒0.28; p=0.03; females: β, 0.07; p=0.48), and inferior frontal gyrus (IFG) volume (males: β, ‒0.28; p=0.02; females: β, 0.10; p=0.33). [Obesity 2024;32:1009-1022]

On the other hand, visceral and subcutaneous adipose tissue exhibited an inverse relationship with middle frontal and superior frontal gyrus volumes in both males and females.

Brain health

“There is a growing body of literature that supports the idea that obesity is associated with brain health outcomes,” Shekhtman said. “Previous research has shown that obesity, primarily measured by BMI, is linked to lower gray matter volume, decreased white matter integrity, and decreased cognitive functioning.” [Physiol Rev 2016;96:1169-1209; Obes Res Clin Pract 2015;9:93-113]

However, evidence regarding the specific associations between abdominal fat depots and brain health outcomes is lacking. In the current study, researchers explored the relationships of four fat depots with cognitive functioning and brain volumes.

“[W]e have found that long-term trajectories of obesity (based on BMI), in older adults with type 2 diabetes, are associated with smaller volumes of the middle temporal gyrus and IFG, which underlies functions of decision-making, attention, and language,” they said. [Diabetologia 2020;63:2446-2451]

In the current middle-aged cohort, researchers also observed associations between abdominal fats and hippocampal, IFG, and middle frontal gyrus volumes. This finding suggests the sensitivity of these brain regions to the harmful effects of fat.

“Overall, our results show that higher pancreatic fat is associated with lower cognitive functioning and lower IFG volume primarily in males, whereas higher pancreatic fat percentage is associated with lower hippocampal volume mostly in females,” the authors said.

“These results suggest that already in midlife, abdominal fat accumulation may have deleterious effects on brain health, especially in men,” they added.

“Further research is needed to confirm these findings and investigate the underlying mechanisms that may explain the observed associations, which may lead to sex-specific interventions for the promotion of brain health,” the authors said.