Association of dietary copper intake with Alzheimer’s disease, brain structure and cognitive function

This study aimed to investigate the relationships between dietary copper intake and the risk of Alzheimer’s disease (AD), cognitive function, and brain structural measures. A combined prospective cohort and cross-sectional analysis. The UK Biobank. This analysis included 126,660 participants (56,053 males and 70,607 females) from the UK Biobank who were free of baseline dementia and had complete dietary data. The mean age at baseline was 56.14 ± 7.83 years, and the median dietary copper intake was 1.33 mg/day (IQR: 1.10–1.61). Dietary copper intake was assessed via 24-h dietary recalls. AD diagnosis was obtained from health records. Cognitive function and brain structural measures were derived from neuropsychological assessments and MRI scans, respectively. Cox proportional hazards models with restricted cubic splines were used to examine associations. Over a median follow-up of 13.34 years, 619 participants developed AD. A nonlinear U-shaped association was observed between copper intake and AD risk (P for nonlinearity <0.001), with the lowest risk at an intake of 1.57 mg/day. Compared to the reference intake (1–2 mg/day), both lower and higher intakes were associated with increased AD risk, with the highest risk at intakes ≥3 mg/day (HR = 2.73, 95% CI: 1.53–4.87). This pattern remained consistent across subgroups stratified by genetic risk. Copper intake also showed significant nonlinear associations with cognitive function and brain structure, with optimal ranges consistently observed between approximately 1.3 and 2.0 mg/day. Dietary copper intake exhibits a U-shaped association with AD risk, and maintaining intake within an appropriate range (approximately 1.3–2.0 mg/day) may help reduce AD risk and benefit cognitive function and brain health.