As the aging population steadily grows and life expectancies increase, age-related dementia is becoming a source of increasing concern because of its increasing burden on health care costs (Yao et al., 2022). In 2019, there were approximately 52 million dementia cases worldwide (Nichols et al., n.d.; Ren et al., n.d.). Cognitive impairment is an intermediate stage between normal aging and dementia, which reduces the capacity for memory, attention, and language and contributes directly to disability in elderly individuals (Xue et al., n.d.). Therefore, disentangling risk factors for cognitive impairment in older adults is highly important. Recently, increasing evidence has suggested that environmental exposure may have a detrimental effect on cognitive function in older adults (Li et al., 2023a; Yu et al., 2023).

At present, metals are the main environmental pollutants that can enter the human body through polluted air and food. Exposure to multiple metals may improve adverse cognitive effects, especially during later life exposure periods with decreased brain function. There is epidemiologic and experimental evidence linking exposure to metals with cognitive function (Li et al., 2023a; Cai et al., 2023), but several important gaps exist. First, although recent epidemiology studies have focused on combined multi-metal exposure and health risks (Xiao et al., 2021; Hou et al., 2019), the potential mechanism of multiple-metal exposure and cognitive impairment is unclear. Second, for precise prevention, the sex and age differences that contribute to environmental and metabolite and cognitive impairment inequalities have become a matter of concern.

Over the past few decades, new high-throughput technologies have emerged, allowing us to study cognitive function, including metabolites, with more molecular scrutiny. Recent studies using metabolomic profiling have revealed an altered lipid profile associated with the development and progression of cognitive impairment (Cordeiro et al., n.d.). In turn, metabolites are also gaining popularity in the field of environmental health research as a cost-efficient means for linking external and internal exposures, biological responses and diseases (Vermeulen, n.d.), and they have shown promise in a few applied studies (Jin et al., n.d.).

It is well known that few studies have attempted to integrate biomarkers of exposure to metals with metabolic biomarkers to uncover signatures with potential effects to provide information about the molecular pathways underlying the progression of cognitive impairment in elderly individuals. In this pilot study, we aimed to explore the potential integration of ultratrace profiling of metal biomarkers and cognitive impairment biomarker profiling (metabolites) in etiological research on cognitive impairment in elderly individuals. We also aimed to determine whether these associations could be potentially modified by sex and age. These results are helpful for identifying metabolite biomarkers of metal exposure and cognitive impairment risk in elderly individuals in eastern China.