Serum clinical laboratory tests and risk of incident dementia: a prospective cohort study of 407,190 individuals

Prevention of dementia is a public health priority, and the identification of potential biomarkers may provide benefits for early detection and prevention. This study investigates the association of common serum laboratory tests with the risk of incident dementia. Among 407,190 participants from the UK Biobank (median follow-up of 9.19 years), we investigated the linear and nonlinear effects of 30 laboratory measures on the risk of all-cause dementia using Cox models and restricted cubic spline models. We found that dementia incidence was associated with low vitamin D concentration (hazard ratio 0.994, 95% confidence interval 0.993-0.996), indicators of endocrine disorders: IGF-1 level (P for non-linearity = 1.1E-05), testosterone level (P for non-linearity = 0.006); high sex-hormone-binding globulin level (HR 1.004, 95% CI: 1.003-1.006); reduced liver function: lower alanine aminotransferase (HR 0.990, 95% CI: 0.986-0.995); renal dysfunction: cystatin C level (P for non-linearity = 0.028); oxidative stress: lower urate level (HR 0.998, 95% CI: 0.998-0.999); lipids dysregulation: lower LDL (HR 0.918, 95% CI: 0.872-0.965) and triglycerides (HR 0.924, 95% CI: 0.882-0.967) concentrations; insulin resistance: high glucose (HR 1.093, 95% CI: 1.045-1.143) and HbA1c (HR 1.017, 95% CI: 1.009-1.025) levels; immune dysbiosis: C-reactive protein (P for non-linearity = 5.5E-09). In conclusion, markers of vitamin D deficiency, GH-IGF-1 axis disorders, bioactive sex hormone deficiency, reduced liver function, renal abnormalities, oxidation, insulin resistance, immune dysbiosis, and lipids dysregulation were associated with incident dementia. Our results support a contributory role of systemic disorders and diverse biological processes to onset of dementia.