MRI-derived body fat distribution patterns—particularly pancreatic-predominant and skinny-fat profiles—were associated with gray matter atrophy, cognitive decline, and elevated neurologic disease risk in a UK Biobank analysis of nearly 26,000 patients published in Radiology.

Using latent profile analysis, researchers identified six fat distribution profiles in both male and female patients: pancreatic-predominant, hepatocyte-predominant, skinny-fat, balanced high adiposity, balanced low adiposity, and lean. The pancreatic-predominant profile showed markedly elevated proton density fat fraction, with mean body mass index (BMI)-adjusted z scores of 2.38 in men and 3.01 in women. The skinny-fat profile demonstrated the highest adiposity burden in the majority of depots despite moderate BMI.

Compared with the lean profile, profiles 1 through 5 generally showed lower total brain volume, lower gray matter volume, and greater white matter hyperintensity volume, though not all pairwise comparisons reached statistical significance. The most pronounced gray matter atrophy was present in the pancreatic-predominant profile for both sexes and in the skinny-fat profile for male patients. Cortical atrophy in these profiles was widespread in anterior brain regions.

Using neurite orientation dispersion and density imaging metrics, male patients showed widespread alterations across profiles, including lower intracellular volume fraction and higher isotropic volume fraction. Female patients showed statistically significant differences in fewer than half of fiber bundle comparisons. Brain age gap also demonstrated sex-specific patterns, with male patients showing higher values across profiles 1 through 4, while female patients showed no statistically significant difference across profiles.

Compared with the lean benchmark, lower psychomotor speed was observed in male patients with profile 1, 3, or 4 and female patients with profile 1, 3, 4, or 5. Poorer prospective memory was found in male patients with profile 1, 2, or 3. Visual memory was lower in male profile 3 and female profile 1, and global cognitive score was lower only in female patients with profile 1.

Elevated risks for mood disorders, including anxiety and depressive disorders, were observed across multiple profiles in both sexes relative to the lean benchmark. Profile 3 (skinny-fat) in male patients and profiles 1, 2, and 3 in female patients were associated with elevated risks for multiple neurologic diseases. A sex-fat distribution interaction was identified only for epilepsy in profile 1.

"Collectively, these exploratory findings highlight the need to look beyond body mass index and to consider fat distribution patterns when assessing neurologic risks," wrote lead study researcher Miao Yu, MD, of the Affiliated Hospital of Xuzhou Medical University in Xuzhou, China, and colleagues.
Disclosures can be found in the published study.

Source: Radiology