Metals linked with the most prevalent primary neurodegenerative dementias in the elderly: A narrative review

Abstract

The ageing population has been steadily increasing worldwide, leading to a higher risk of cognitive decline and dementia. Environmental toxicants, particularly metals, have been identified as modifiable risk factors for cognitive impairment. Continuous exposure to metals occurs mainly through dietary sources, with older adults being particularly vulnerable. However, imbalances in the gut microbiota, known as dysbiosis, have also been associated with dementia. A literature review was conducted to explore the potential role of metals in the development of cognitive decline and the most prevalent primary neurodegenerative dementias, as well as their interaction with the gut microbiota. High levels of iron (Fe) and copper (Cu) are associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), while low selenium (Se) levels are linked to poor cognitive status. Parkinson's disease dementia (PDD) is associated with elevated levels of iron (Fe), manganese (Mn), and zinc (Zn), but the role of copper (Cu) remains unclear. The relationship between metals and Lewy body dementia (LBD) requires further investigation. High aluminium (Al) exposure is associated with frontotemporal dementia (FTD), and elevated selenium (Se) levels may be linked to its onset. Challenges in comparing studies arise from the heterogeneity of metal analysis matrices and analytical techniques, as well as the limitations of small study cohorts. More research is needed to understand the influence of metals on cognition through the gut microbiota (GMB) and its potential relevance in the development of these diseases.