Blood Manganese Exposure and Risk of Cognitive Impairment in Older Adults: Evidence from Prospective Cohort Study.

Abstract

Objective: The prospective cohort study aimed to examine the link between blood Manganese (Mn) concentrations and incident cognitive impairment risk in Chinese elderly individuals.

Methods: This study enrolled 6,868 individuals aged 60 years and above from two cohort studies from 2017 to 2024. High-resolution inductively coupled plasma mass spectrometry was employed to quantify blood Mn concentrations. Cognitive function was evaluated by Mini-Mental State Examination (MMSE). Cox proportional hazards models were used to assess the association between blood Mn levels and risk of cognitive impairment, while linear mixed-effects models were used to examine their associations with MMSE and domain-specific cognitive scores. Restricted cubic spline (RCS) was confirmed to explore the dose-response relationship.

Results: During an average follow-up of 4.00 years, 1,138 developed cognitive impairment. The mean blood Mn concentration across all participants was 11.297 ± 3.763 µg/L. After full adjustment for covariates, higher blood Mn levels (per interquartile range [ IQR] increase) were significantly associated with greater declines in MMSE score ( β = -0.033, 95% confidence interval [ CI]: -0.048, -0.018) and in multiple domain-specific scores, including orientation, attention and calculation, language, naming, and recall, with the strongest associations observed for naming ( β = -0.043, 95% CI: -0.070, -0.015) and recall ( β = -0.047, 95% CI: -0.064, -0.030). Individuals in the highest quartile ( Q ₄ ) of blood Mn levels exhibited a 28.5% greater risk of cognitive impairment (Adjusted hazard ratio [ HR] =1.285, 95% CI: 1.081, 1.526) versus the lowest quartile ( Q ₁) of blood Mn levels. The risk of cognitive impairment was 13.1% higher for each IQR increase in blood Mn ( HR = 1.131, 95% CI: 1.051, 1.217). A positive and linear dose-response pattern was confirmed by the RCS model ( P for non-linearity > 0.05).

Conclusions: In this population-based prospective cohort study of older adults, higher blood Mn levels were significantly associated with poorer cognitive performance and an increased risk of cognitive impairment, with the most pronounced associations observed for naming and recall ability, suggesting that reducing Mn exposure could serve as a modifiable target for cognitive health protection among older adults.