A neural signature of metabolic syndrome

Eithan Kotkowski, Larry R. Price, Crystal Franklin, Maximino Salazar, Mary Woolsey, Ralph A. DeFronzo, John Blangero, David C. Glahn, Peter T. Fox

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


That metabolic syndrome (MetS) is associated with age-related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray-matter volume (GMV) using a cross-sectional, between-group contrast design in a large, ethnically homogenous sample. T1-weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican-American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age- and sex-matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole-brain, voxel-wise manner using voxel-based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half-sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.

Original languageEnglish (US)
Pages (from-to)3575-3588
Number of pages14
JournalHuman Brain Mapping
Issue number12
StatePublished - Aug 15 2019
Externally publishedYes


  • GOBS
  • MetS
  • Mexican-American
  • T2DM
  • Type II diabetes mellitus
  • VBM
  • genetics of brain structure
  • gray matter volume
  • hypercholesterolemia
  • hyperglycemia
  • hypertension
  • hypertriglyceridemia
  • insulin resistance
  • insulin resistance syndrome
  • metabolic syndrome
  • neuroimaging
  • obesity
  • voxel-based morphometry
  • waist circumference

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Anatomy


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