To investigate the relationship between a metabolic signature indicative of a healthy lifestyle and dementia risk, and the mediating role of structural brain impairment.
Key Findings:
Identified 83 metabolites associated with a healthy lifestyle.
Each standard deviation increment in metabolic signature correlated with a lower risk of all-cause dementia (HR 0.89).
Mendelian randomization indicated potential causal links between metabolites and dementia risk.
Structural brain reserve, particularly in the hippocampus, mediated 6.21% to 11.98% of the relationship between metabolic signature and dementia risk.
Interpretation:
A healthy lifestyle metabolic signature is inversely associated with dementia risk, with structural brain reserve playing a significant mediating role.
Limitations:
Study design is observational, limiting causal inference.
Potential biases in self-reported lifestyle data.
Generalizability may be limited to the UK population.
Conclusion:
The findings underscore the importance of a healthy lifestyle in reducing dementia risk and highlight the role of brain structure in this relationship.
