Associations between Metals, Serum Folate, and Cognitive Function in the Elderly: Mixture and Mediation Analyses

Area of Science:

• Environmental Health
• Neuroscience
• Gerontology

Background:

• Metal exposure's impact on elderly cognitive health is debated.
• The role of serum folate in metal-cognitive health relationships is unclear.
• Understanding these associations is crucial for public health interventions.

Purpose of the Study:

• To evaluate the individual and joint effects of metals on cognitive function in US elderly.
• To explore the potential mediating role of serum folate in metal-cognitive associations.
• To analyze metal mixtures and their impact on cognitive performance.

Main Methods:

• Utilized NHANES 2011-2014 data from 2002 participants aged 60+.
• Measured blood metal concentrations using inductively coupled plasma mass spectrometry (ICP-MS).
• Assessed cognitive function via Immediate Recall (IRT), Delayed Recall (DRT), Animal Fluency (AFT), and Digit Symbol Substitution (DSST) tests.
• Employed Generalized Linear Models (GLMs), Bayesian Kernel Machine Regression (BKMR), and Quantile G-computation (QG-C) for statistical analysis.
• Conducted mediation analyses to investigate serum folate's role.

Main Results:

• Cadmium exposure showed a negative association with Immediate Recall test (IRT) and Digit Symbol Substitution test (DSST) z-scores.
• High selenium levels were significantly associated with better cognitive performance across multiple models.
• Serum folate partially mediated the effects of cadmium and selenium on DSST z-scores (17% and 10% mediation, respectively).

Conclusions:

• High selenium is linked to enhanced cognitive function in the elderly, while cadmium is associated with cognitive decline.
• Serum folate may play a partial mediating role in the relationship between cadmium, selenium, and working memory.
• Findings highlight the complex interplay between metal exposure, serum folate, and cognitive health in older adults.