Neuroticism, omega-3 fatty acids, and risk of incident dementia.
Gao Y., van Duijn C., Littlejohns TJ., Amin N.
BACKGROUND: High levels of neuroticism are associated with an increased risk of dementia, yet the underlying biological mechanisms remain poorly understood. Investigating the role of metabolites, the downstream products of metabolic processes, may offer valuable insights into this association. METHODS: In 215,624 dementia-free UK Biobank participants aged 40-69 years, we assessed neuroticism's associations with 249 nuclear magnetic resonance-measured metabolites using linear regression. Metabolites reaching Bonferroni-corrected significance were further tested for associations with incident all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD) using Cox proportional-hazards regression, and with white matter hyperintensities volume using linear regression. Causality in significant observational relationships was evaluated through two-sample Mendelian randomization. RESULTS: Neuroticism was significantly associated with 119 out of 249 metabolites (Bonferroni-adjusted p