Trace elements and cognition in the general population: The HUNT study

Trace elements play essential roles in neurobiology, but evidence linking whole blood concentrations to cognitive outcomes in the general population remains limited. This study examined whether concentrations of eight trace elements: selenium, mercury, cadmium, arsenic, lead, manganese, copper, and zinc were associated with cognitive performance assessed approximately six years later in a Norwegian general population cohort from the HUNT3 Survey.

Whole blood trace element concentrations were measured using high resolution inductively coupled plasma mass spectrometry, with several strategies to minimize contamination. General cognitive performance was assessed using a validated web-based cognitive test battery capturing processing speed, motor speed, attention, and episodic and working memory. Associations were estimated using linear models with restricted cubic splines, adjusting for age, sex, and education.

The sample included 252 participants aged 50-65 years (43% women), generally characterized by good somatic and mental health. No associations were observed for selenium, mercury, cadmium, arsenic, lead, manganese, or copper. Zinc showed a shallow U-shaped association, with slightly lower cognitive performance at mid-range concentrations, although the effect size was small. Cognitive performance declined with age and increased with educational attainment.

In this low-exposure general population, whole blood trace elements concentrations showed no meaningful associations with cognitive performance six years later. These findings suggest that exposure levels to non-essential trace elements in this cohort are too low to exert clinically relevant effects on cognitive health. Alternatively, single time-point whole blood measurements may not reflect cumulative exposure relevant to long-term cognitive outcomes, or the study was underpowered to detect modest associations.