Investigating the Causal Relationship between Neuroticism and Alzheimer's Disease Using Mendelian Randomization and the Mediating Role of Modifiable Risk Factors

The study investigated the relationship between neuroticism (a personality trait characterized by a predisposition to experience intense and frequent negative emotions) and Alzheimer's disease. Using Mendelian randomization based on genome-wide association study data, researchers found that a direct causal relationship between neuroticism and Alzheimer's disease is unlikely. The analysis included 121,825 control participants and 1,277 individuals with Alzheimer's disease from the UK Biobank aged 60 years and older. Depression, hypertension, and alcohol consumption were identified as significant mediators of the relationship between higher neuroticism and increased Alzheimer's disease risk. The results suggest that the association between neuroticism and Alzheimer's disease is explained more by modifiable health and behavioral factors rather than by a direct causal effect.