Environmental Metals in Urine: What’s the Link to Cognition and Dementia Risk?

A higher concentration of environmental metals in urine is associated with worse cognitive performance and an increased risk for dementia, according to the findings of a study published in JAMA Network Open.

Environmental metals have neurotoxic effects at high levels. However, research into their neurotoxic effects at low levels has been limited.

Researchers from Columbia University Mailman School of Public Health sourced data for this study from the Multi-Ethnic Study of Atherosclerosis (MESA), which was a multicenter, prospective cohort study conducted at 6 sites in the United States from 2000 to 2018. Participants (N=6303; mean age, 60 years; women, 52.4%) who had a urinary metal assessment at baseline were evaluated for dementia onset and the longitudinal change in cognitive scores.

The study participants had a body mass index (BMI) of 27.5 (24.5-31.1) kg/m², 36.4% had high school or less education, and 72.3% did not carry an apolipoprotein E4 (APOE4) allele. They were free of diagnosed cardiovascular disease.

During a median follow-up of 16.7 years, 559 individuals were diagnosed with dementia.

Longitudinal changes in Digit Symbol Coding (DSC) z-scores were negatively associated with urinary levels of arsenic (mean difference [MD], -0.03), cobalt (MD, -0.05), copper (MD, -0.05), uranium (MD, -0.04), and zinc (MD, -0.03).

Stratified by APOE4 status, noncarriers had significant associations between the change in DSC z-score and urinary levels of arsenic (MD, -0.041), cobalt (MD, -0.041), and copper (MD, -0.055) whereas carriers had significant associations with urinary levels of cobalt (MD, -0.084), copper (MD, -0.050), manganese (MD, -0.066), uranium (MD, -0.073), and zinc (MD, -0.078). Significant APOE4 interactions were observed with manganese (P =.02) and zinc (P =.03).

Dementia risk was associated with every one-IQR increase in urinary cadmium (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.15-1.68), copper (aHR, 1.20; 95% CI, 1.06-1.37), uranium (aHR, 1.74; 95% CI, 1.14-2.65), and zinc (aHR, 1.34; 95% CI, 1.07-1.67) among noncarriers and with tungsten (aHR, 1.24; 95% CI, 1.03-1.49) and zinc (aHR, 1.24; 95% CI, 1.03-1.49) among carriers.

In the pooled study population, there was an associated increased risk for dementia for every 1-IQR increase in:

• urinary arsenic (aHR, 1.32; 95% CI, 1.07-1.65),
• cadmium (aHR, 1.17; 95% CI, 1.01-1.36),
• cobalt (aHR, 1.18; 95% CI, 1.01-1.38),
• copper (aHR, 1.16; 95% CI, 1.05-1.28),
• tungsten (aHR, 1.15; 95% CI, 1.03-1.29),
• uranium (aHR, 1.46; 95% CI, 1.06-2.02), and
• zinc (aHR, 1.35; 95% CI, 1.13-1.61).

Using a mixture of metals, individuals with metal levels in the 95^th percentile were at increased risk for dementia relative to those in the 25^th percentile (hazard ratio [HR], 1.71; 95% CI, 1.24-3.89). Stratified by APOE4 status, high metal levels associated with increased risk for dementia among noncarriers (HR, 3.03; 95% CI, 1.39-6.22) but not among carriers (HR, 1.70; 95% CI, 0.67-3.92).

This study may have been limited by relying on medical coding for dementia diagnoses, which may have included individuals with memory loss and not dementia.

“[W]e found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.