Abstract
OBJECTIVES: Diabetes was associated with increased serum urate levels and a higher risk of dementia. However, current evidence regarding the association between serum urate and dementia is controversial.The research gap on how to effectively control urate levels in the population with diabetes still remains. We aim to examine the association of diabetes status and serum urate with dementia incidence, and the differences in this association among participants with different diabetes statuses. METHODS: A total of 321,896 participants was recruited from the UK Biobank and followed up until 2022. Diabetes status was classified into diabetes, prediabetes and normoglycaemia according to the American Diabetes Association 2023 guideline. Serum urate levels were stratified using gender-specific quartiles of concentrations. All-cause dementia, Alzheimer's disease and vascular dementia were ascertained using the International Classification of Diseases-10th revision (ICD-10). Cox proportional hazards regression models were used to examine the association between serum urate, diabetes status, and dementia incidence. RESULTS: Of the 321,896 participants (mean age, 57 years old; 43.5% males), 7,087 (2.20%) individuals were diagnosed with dementia during the follow-up period. Diabetes was associated with a 70% 58%, and 134% increased risk for all-cause dementia, Alzheimer's disease, and vascular dementia respectively. Elevated serum urate levels were associated with a lower risk of all-cause and cause-specific dementia regardless of the status of diabetes. Each standard deviation increase in urate concentration was related to a 11% reduced risk for all-cause dementia (HR, 0.89; 95% CI, 0.86 to 0.91), 7% for Alzheimer's disease (HR, 0.93; 95% CI, 0.88 to 0.98), and 12% for vascular dementia (HR, 0.88; 95% CI, 0.81 to 0.95). CONCLUSION: Appropriately higher urate levels within the threshold of hyperuricemia can reduce the adverse health effects of excessively high urate levels and better protect the cognitive health of people with varying diabetes status.