Metabolic syndrome is associated with accelerated brain aging

INTRODUCTION: Metabolic syndrome (MetS) is associated with increased dementia risk, but its relationship with brain aging is unclear. METHODS: The study included 27,375 UK Biobank participants aged 40 to 70 years. MetS was defined as having at least three of five components: central adiposity, hypertension, dyslipidemia, hypertriglyceridemia, and hyperglycemia. Levels of 33 plasma metabolites were measured from baseline blood samples. Brain age was estimated using a machine learning model based on 1079 phenotypes from brain magnetic resonance imaging (MRI) scans and used to calculate brain age gap (BAG, i.e., brain age minus chronological age). RESULTS: Participants with MetS had significantly higher BAG compared to MetS-free individuals (β = 1.13; 95% confidence interval [CI]: 0.99 to 1.27). Each individual MetS component was also associated with higher BAG. Eight metabolites significantly mediated the MetS-BAG association (mediation proportion: 2.6% to 16.5%), including apolipoproteins, fatty acids, and inflammatory markers. DISCUSSION: MetS is associated with accelerated brain aging, partly mediated by inflammation and altered lipid metabolism.