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

Abstract

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 β: -0.06; 95% CI -0.08, -0.04), gray matter (β: -0.10; 95% CI -0.12, -0.08) and hippocampal (for left side, β: -0.03, 95% CI -0.05, -0.01; for right side, β: -0.04, 95% CI -0.07, -0.02) volumes, and greater white matter hyperintensity (WMH) volume (β: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (β: -0.10; 95% CI -0.13, -0.07), verbal declarative memory (β: -0.08; 95% CI -0.11, -0.05), processing speed (β: -0.06; 95% CI -0.09, -0.04), verbal and numerical reasoning (β: -0.07; 95% CI -0.09, -0.04), nonverbal reasoning (β: -0.03; 95% CI -0.05, -0.01), and on tests of executive function, where higher scores indicated poorer performance (β: 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.

Graphical abstract

Figure 1

Multivariable linear regression analyses examining the association between the number of MetS components and standardized neuroimaging measures. A: Total brain volume. B: Gray matter volume. C: White matter volume. D: Left hippocampal volume. E: Right hippocampal volume. F: WMH volume. Models were adjusted for age, sex, age², age × sex, age² × sex, ethnicity, education level, Townsend deprivation index, household income, alcohol intake, smoking status, physical activity level, APOE-ε4 carrier status, assessment center, time between baseline and follow-up imaging assessment, head size, head size, head position, and head motion. WMH was log-transformed. All outcomes were standardized (mean = 0; SD = 1) to permit comparison of effect size across outcomes. Red denotes unfavorable direction (i.e., potential challenge or risk to brain health). Blue denotes favorable direction (i.e., potential neutral or protective effect on brain health).

Figure 2

Multivariable linear regression analyses examining the association between the number of MetS components and standardized cognitive test scores. A: Executive function (TMT A). B: Executive function (TMT B). C: Verbal and numerical reasoning (FI); D: Working memory (BDS); E: Processing speed (SDS). F: Verbal declarative memory (PAL). G: Nonverbal reasoning (MPC). Models were adjusted for age, sex, age², age × sex, age² × sex, ethnicity, education level, Townsend deprivation index, household income, alcohol intake, smoking status, physical activity level, APOE-ε4 carrier status, assessment center, and time between baseline and follow-up imaging assessment. TMT A and B were log-transformed. All outcomes were standardized (mean = 0; SD = 1) to permit comparison of effect size across outcomes. Red denotes poor performance (i.e., potentially indicative of challenges in cognitive function). Blue denotes good performance. BDS, backward digit span task; FI, Fluid Intelligence Score; MPC, matrix pattern completion test; PAL, paired associate learning task; SDS, symbol digit substitution task.