Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study

Abstract

Background: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk.

Methods: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors.

Results: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 μmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77).

Conclusions: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.

Keywords: Alzheimer’s dementia; Dementia; Metabolic syndrome; Risk factors; Serum uric acid; Vascular dementia.

Fig. 1

Participant inclusion flow diagram

Fig. 2

Subgroup analyses of metabolic syndrome components and dementia risk. ^a Subgroup analyses stratified by age, gender, and UK Biobank assessment centers. Adjusted for various factors, including race, deprivation index, lifestyle habits, and medication history

Fig. 3

Non-linear association between metabolic syndrome components and all-cause dementia risk. Restricted cubic spline models, with knots at the 10th, 50th, and 90th percentiles, were employed. Reference levels (HR fixed at 1.0) for each plot: A BMI: 27.42 kg/m²; B cholesterol: 5.69 mmol/L; C HDL: 1.45 mmol/L; D LDL: 3.56 mmol/L; E glucose: 5.12 mmol/L; F HbA1c: 36.08 mmol/L; G SBP: 139.6 mm Hg; H DBP: 82.25 mm Hg; I WC: 90.27 cm; J TG: 1.74 mmol/L Adjustments were made for age, gender, and UK Biobank assessment centers. Additional adjustments included race, index of multiple deprivation, smoking status, alcohol consumption, physical activity, portions of fruit and vegetable intake, regular medications (multivitamin use, mineral supplement, non-steroidal anti-inflammatory drugs, and aspirin), and history of dementia