Visceral Fat Has Link to Brain Volume

Middle-age patients with lots of visceral fat may have low brain volume, researchers say.

In a cross-sectional study, visceral fat was significantly associated with lower total brain volume, even when controlling for body mass index (P=0.02) and insulin resistance (P=0.01), Sudha Seshadri, MD, of Boston University, and colleagues reported online in the Annals of Neurology.

"Our data suggest that the association is stronger for central obesity versus global adiposity and is particularly prominent and robust for the visceral fat component of abdominal obesity," they wrote.

Obesity in midlife has been associated with an increased risk of dementia, but the underlying mechanisms are poorly understood.

Studies have shown that different fat compartments carry different metabolic risks. For example, there's growing evidence that abdominal obesity and visceral fat have a stronger relationship with vascular risk than global BMI.

So to examine the relationship between measures of body mass and brain volume in middle-age, the researchers looked at 733 patients, mean age 60, from the Framingham Offspring cohort, who'd had an MRI to assess brain volume.

Overall, they found that greater BMI, waist circumference, waist-hip ratio, and subcutaneous and visceral adipose tissue were associated with lower total brain volume, regardless of vascular risk factors.

The association between visceral fat and brain volume was the strongest and most robust, they said, and was also independent of BMI and insulin resistance.

However, all of the associations were attenuated and were no longer statistically significant after adjusting for C-reactive protein levels.

Also, there were no associations between abdominal fat measures and temporal horn volume, white matter hypersensitivity volume, or brain infarcts.

Zaven S. Khachaturian, PhD, of the Campaign to Prevent Alzheimer's Disease by 2020 and the former director of the office of Alzheimer's research at the National Institutes of Health, said the findings are preliminary because they "merely establish a correlation" between brain volume and obesity.

"This needs to be studied further," he told MedPage Today, adding that one of the primary values of the research by Seshadri and colleagues is "opening new ideas for studies."

For instance, the "relationship between obesity and brain changes may be mediated through vascular pathology," and that should be investigated further, he said.

But Khachaturian cautioned that physicians should not yet suggest that reducing weight will decrease risk of Alzheimer's disease.

"You want people to control their weight for other reasons, such as the relationship with diabetes and vascular disease," he said. "You can't use this study to say, 'Reduce your weight and that will reduce Alzheimer's.' That relationship is tenuous."

"We need to understand [the relationship] before we can make recommendations," Khachaturian added.

In their paper, Sheshadri and colleagues wrote that the mechanisms underlying the relationship are speculative.

Inflammation could be an important mediator, they suggested, as obesity is highly associated with inflammatory markers. Cytokines such as interleukin-6 and tumor necrosis factor alpha, for example, are produced in adipose tissue, and it also contains inflammatory monocytes and macrophages.

Diabetes and insulin resistance are other potential mediators, the researchers noted, but their results imply that they are not the sole mediators.

Their results also imply that global brain atrophy could be the main mechanism behind the association between BMI and cognitive decline and dementia, rather than vascular brain injury.

Still, further study is needed, the researchers acknowledged, since theirs was limited by its cross-sectional design, which can't establish causation, by a lack of a direct measurement of hippocampal volume, as well as by absence of longitudinal measurements.