Obesity and metabolic syndrome and functional and structural brain impairments in adolescence

Abstract

Background: The prevalence of metabolic syndrome (MetS) parallels the rise in childhood obesity. MetS is associated with neurocognitive impairments in adults, but this is thought to be a long-term effect of poor metabolism. It would be important to ascertain whether these brain complications are also present among adolescents with MetS, a group without clinically manifest vascular disease and relatively short duration of poor metabolism.

Methods: Forty-nine adolescents with and 62 without MetS, matched on age, socioeconomic status, school grade, gender, and ethnicity, received endocrine, MRI, and neuropsychological evaluations.

Results: Adolescents with MetS showed significantly lower arithmetic, spelling, attention, and mental flexibility and a trend for lower overall intelligence. They also had, in a MetS-dose-related fashion, smaller hippocampal volumes, increased brain cerebrospinal fluid, and reductions of microstructural integrity in major white matter tracts.

Conclusions: We document lower cognitive performance and reductions in brain structural integrity among adolescents with MetS, thus suggesting that even relatively short-term impairments in metabolism, in the absence of clinically manifest vascular disease, may give rise to brain complications. In view of these alarming results, it is plausible that obesity-associated metabolic disease, short of type 2 diabetes mellitus, may be mechanistically linked to lower the academic and professional potential of adolescents. Although obesity may not be enough to stir clinicians or even parents into action, these results in adolescents strongly argue for an early and comprehensive intervention. We propose that brain function be introduced among the parameters that need to be evaluated when considering early treatment of childhood obesity.

FIGURE 1

Representative clusters of lower WM FA value among adolescents with MetS. Each column displays 1 cluster of FA reduction in axial, coronal, and sagittal orientations with the axes going through the cluster centroid. Cluster size (minimum 100 voxels, equivalent to 0.1 mL in volume) is shown in parentheses.

FIGURE 2

Lower cognitive performance with increasing number of MetS components present. A, WRAT arithmetic standard score. B, WRAT spelling standard score. C, Trails B total time. D, DVT total time for individuals who met 0 criterion (n = 21), 1 criterion (n = 18), 2 criteria (n = 23), 3 criteria (n = 36), or 4+ criteria (n = 13). Data presented are mean ± SEM.

FIGURE 3

Lower QUICKI scores (more IR) were associated with smaller ICV-adjusted hippocampal volumes (n = 91) (A) and larger ICV-adjusted overall CSF volumes (n = 92) (B).