A Latent Clinical-anatomical Dimension Relating Metabolic Syndrome to Brain Morphology: Evidence from a Multivariate Imaging Analysis of 40,087 Individuals.

Metabolic syndrome (MetS) describes the clustered prevalence of abdominal obesity, arterial hypertension, dyslipidemia and insulin resistance, collectively promoting cerebrovascular disease. Although this risk factor complex causes a substantial health burden in modern societies, its neural underpinnings remain elusive. To investigate the multivariate association of MetS and cortical thickness, we applied partial least squares (PLS) correlation to a pooled sample of two large-scale population-based cohort studies totaling 40,087 individuals. PLS identified a latent clinical-anatomical dimension relating more severe MetS with a widespread pattern of cortical thickness abnormalities and worse cognitive performance. MetS effects were strongest in regions with high density of endothelial cells, microglia and excitatory neurons of subtype 8. Moreover, regional MetS effects correlated within functionally and structurally connected brain networks. Overall, our research suggests a low-dimensional relationship between MetS and brain structure that is governed by both the microscopic composition of brain tissue as well as macroscopic brain network organization.