Associations between essential trace elements and Alzheimer's disease and related dementias.

INTRODUCTION: Dysregulation of essential trace elements has been implicated in Alzheimer's disease (AD) pathogenesis, yet comprehensive epidemiologic evidence remains limited. We investigated associations of seven plasma essential trace elements, including manganese, iron, cobalt, copper, zinc, selenium, and molybdenum, with AD and all-cause dementia risk. METHODS: We analyzed 1,737 participants from the National Alzheimer's Coordinating Center. Cross-sectional analyses assessed prevalent disease; longitudinal analyses evaluated incident cases among 1,101 initially dementia-free participants (median follow-up: 2.05 years). Multivariable logistic regression, Cox proportional hazards models, and quantile-based g-computation evaluated individual and mixture effects. RESULTS: A simultaneous one-quartile increase in the seven-element mixture was associated with lower prevalent AD (odds ratio [OR] = 0.69; 95% confidence interval [CI]: 0.52-0.91). Longitudinally, higher plasma iron was associated with lower incident AD (hazard ratio [HR] = 0.41; 95% CI: 0.19-0.92, Q4 vs. Q1), while selenium predicted higher incident AD risk (HR = 2.42; 95% CI: 1.11-5.27, Q4 vs. Q1). DISCUSSION: Lower plasma iron and higher plasma selenium were each associated with greater dementia risk, identifying iron and selenium as potentially modifiable factors for dementia prevention, especially in selenium-replete populations.