Association of circulating branched-chain or aromatic amino acids based on metabolome and apolipoprotein E genotype with incident dementia: a large cohort study

The associations between branched-chain amino acids (BCAAs) and dementia in individuals with chronic diseases remain unclear, and evidence on aromatic amino acids (AAAs) is limited. Using metabolic biomarker data from 117,892 UK Biobank participants, we found that higher circulating levels of BCAAs (HR=0.56, 95% CI: 0.41-0.76) and AAAs (HR=0.74, 95% CI: 0.55-0.98) were associated with lower risks of all-cause dementia and Alzheimer's disease, but not vascular dementia. Stratified analyses showed stronger inverse associations for BCAAs among women and individuals without diabetes (both P for interaction = 0.001). Similarly, AAAs were inversely associated with dementia risk primarily in non-diabetic participants, but not modified by hypertension or dyslipidemia. These findings highlight the potential protective roles of BCAAs and AAAs and underscore the importance of sex and diabetes status in dementia prevention.