A study published in the Journal of the American Medical Association examined the relationship between urinary metal levels and cognitive decline, with a particular focus on dementia risk. Conducted within a multiethnic cohort, it assesses how both essential and nonessential metals affect cognitive performance, using various cognitive tests like the DSC (digit symbol substitution), CASI (cognitive assessment scale for the elderly), and DS (digit span). The study found significant associations between baseline urinary levels of metals and cognitive decline and highlights potential interactions with genetic factors, specifically the APOE4 allele, which is known to increase Alzheimer’s disease (AD) risk.
The study found that participants who developed dementia had a higher baseline concentration of metals like arsenic, cobalt, lead, manganese, and zinc. These participants were also generally older, had lower education levels, and had lower eGFR (estimated glomerular filtration rate), a measure of kidney function. The study found a strong inverse association between baseline metal levels and cognitive performance, particularly for the DSC test, which measures the speed of mental processing. For some metals, the association appeared to follow a nonlinear pattern, with cognitive decline becoming apparent only after a certain threshold of metal exposure.
The key finding of the study was that higher levels of metals were associated with worse cognitive function, as measured by the DSC test. The metals studied included both essential metals, such as zinc and copper, and nonessential metals, like arsenic, cadmium, and lead. Of particular note, there were interactions between the metal exposures and the APOE4 allele, a known genetic risk factor for Alzheimer's disease. The effects of metals on cognitive performance were less pronounced in individuals carrying the APOE4 allele compared to noncarriers, suggesting a potential genetic susceptibility to the harmful effects of metals.
The study also found that higher levels of metals like arsenic, cadmium, cobalt, copper, and zinc were associated with an increased risk of developing dementia. For instance, an interquartile range increase in arsenic levels was associated with a 32% higher risk of dementia, while similar associations were found for other metals like cadmium and copper.
The findings also highlight the complex interplay between genetic and environmental factors in shaping cognitive health. Further studies, particularly experimental studies that directly assess gene-environment interactions, would be beneficial in exploring the mechanisms underlying these associations and developing targeted prevention strategies for at-risk populations.
Sources: Journal of the American Medical Association
