A significant inverse association between anthropometric and computed tomography (CT)–based measurements of abdominal obesity, especially visceral fat, and total brain volume has been observed in healthy middle-aged participants in the Framingham Offspring cohort.

In a study published online in the May 20 issue of the Annals of Neurology, Stephanie Debette, MD, PhD, Boston University School of Medicine in Massachusetts, and multicenter colleagues found that higher body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and radiography-based measurements of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were associated with smaller total cerebral brain volume (TCBV), as measured by magnetic resonance imaging (MRI).

“The thing that is new about this study is that we had CT measurements which were able to define the location of fat as either subcutaneous or visceral, and we found that visceral fat is the one that is associated with a smaller brain,” Sudha Seshadri, MD, Boston University School of Medicine, told Medscape Neurology. “Our results confirm the inverse association of increasing BMI with lower brain volumes in older adults and in younger middle-aged adults and extends the findings to a much larger study sample.”

Cross-Sectional Association
Investigators examined the cross-sectional association of BMI, WC, WHR, and radiography-based measurements of SAT and VAT with MRI measurements of the brain in a sample of 733 community participants (mean age, 60 years), approximately half of whom were female.

Using multivariate linear regression that adjusted for age, sex, and interval between abdominal CT and brain MRI, they found an inverse association of brain size with BMI, WC, WHR, SAT, and VAT, independent of vascular risk factors.

“The association between VAT and TCBV was the strongest and most robust and was also independent of BMI (−0.35 ± 0.15, P = .02)...and insulin resistance (−0.32 ± 0.13, P = .02),” the study authors said.

In contrast, the inverse associations of all adiposity measurements with TCBV were no longer significant when adjusted for C-reactive protein levels, the study authors add. No consistently significant association was identified between anthropometric or CT-based abdominal fat measurements and temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts.

In addition to key inverse associations, investigators found that WHR — but not BMI, WC, SAT, or VAT — was associated with increasing THV, again independently of vascular risk factors.

In contrast, none of the anthropometric measurements of adipose tissue were significantly associated with WMHV, extensive WMHV, or MRI-defined brain infarcts.

As the investigators point out, potential mechanisms underlying the inverse association between obesity — particularly visceral obesity — and total brain volume are speculative but could potentially be mediated by inflammation.

“Obesity is highly associated with inflammatory markers,” they observe. Several different inflammatory markers were recently shown to be inversely associated with TCBV in the Framingham Offspring Study (Neurology. 2007;68:1032-1038).

Diabetes and insulin resistance may also potentially mediate the inverse association between adiposity and brain volume, they add, as again, an inverse association among diabetes, fasting glucose, HOMA-IR (homeostasis model assessment of insulin resistance), and TCBV has similarly been observed in the same cohort.

Lastly, adipose tissue–derived hormones may play a role in the relationship between adipose tissue and brain atrophy. Visceral fat, for example, is more likely to mediate insulin resistance, they point out, and it has a specific pattern of adipose tissue–derived hormone secretion, which could partly explain the stronger inverse association of visceral adipose tissue with total brain volume.

“We know that having a smaller brain is associated with a higher risk of subsequent dementia, so I think it’s just another piece that suggests that vascular and metabolic risk factors like obesity are bad for the brain, and it’s just 1 more reason to try to stay within the normal BMI and avoid abdominal obesity,” Dr. Seshadri concluded.

Important Observations

David Knopman, MD, Mayo Clinic, Rochester, Minnesota, and deputy editor of Neurology, told Medscape Neurology that the observations made by Dr. Debette and colleagues are “important” in that they relate to the bigger picture of how vascular risk factors, especially diabetes, hypertension, and inflammation, in midlife affect brain integrity. “In this particular study, they not only looked at adiposity tissue in a novel way but they had high-quality imaging, which really adds new insights into the risks of midlife obesity and other vascular risk factors.”

And he agreed with the study authors that preservation of brain integrity is yet another reason to hold the waist line in check.

The study was supported by the Framingham Heart Study’s National Heart, Lung, and Blood Institute as well as grants from the National Institute of Neurological Disorders and Stroke and from the National Institute on Aging. Dr. Debette received an award from the Bettencourt-Schueller Foundation. The study authors have disclosed no relevant financial relationships.

Ann Neurol. Published online May 20, 2010.
Pam Harrison - From Medscape Medical News