Association of Metabolic Syndrome With Neuroimaging and Cognitive Outcomes in the UK Biobank

OBJECTIVE Metabolic syndrome (MetS) has been linked to dementia. In this study, we examined the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the impact of MetS on brain health prior to dementia onset. RESEARCH DESIGN AND METHODS We included 37,395 dementia-free adults from the UK Biobank database. MetS was defined as having at least three of the following components: larger waist circumference; elevated levels of triglycerides, blood pressure, HbA1c; or reduced HDL cholesterol levels. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. RESULTS MetS was associated with lower total brain (standardized beta: -0.06; 95% CI -0.08, -0.04), gray matter (beta: -0.10; 95% CI -0.12, -0.08) and hippocampal (for left side, beta: -0.03, 95% CI -0.05, -0.01; for right side, beta: -0.04, 95% CI -0.07, -0.02) volumes, and greater white matter hyperintensity (WMH) volume (beta: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (beta: -0.10; 95% CI -0.13, -0.07), verbal declarative memory (beta: -0.08; 95% CI -0.11, -0.05), processing speed (beta: -0.06; 95% CI -0.09, -0.04), verbal and numerical reasoning (beta: -0.07; 95% CI -0.09, -0.04), nonverbal reasoning (beta: -0.03; 95% CI -0.05, -0.01), and on tests of executive function, where higher scores indicated poorer performance (beta: 0.05; 95% CI 0.03, 0.08). More MetS components were also associated with less brain volume, greater WMH, and poorer cognition across all domains. CONCLUSIONS MetS was associated poorer brain health in dementia-free adults, characterized by less brain volume, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health.