Environmental aluminum exposure and Alzheimer's disease risk: Evidence from a systematic review and meta-analysis

Aluminum (Al) is a widespread environmental contaminant with suspected links to neurodegenerative diseases, particularly Alzheimer's disease (AD). This systematic review and meta-analysis aimed to evaluate the association between environmental Al exposure and the risk of AD by synthesizing evidence from diverse sources and study designs. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature searches were performed in PubMed, Scopus, Web of Science, EMBASE, and the gray literature up to June 2024. After duplicate removal and screening of 6504 records, 54 eligible studies on Al exposure and dementia/AD were included. Data extraction focused on exposure media, Al concentrations, Al and AD/dementia correlation, and geographic context. Screening was independently conducted by two reviewers, with good inter-rater reliability (Kappa = 0.75). Meta-analysis was conducted on the studies that reported sufficient quantitative data, using Hedges' g to estimate the effect size of Al exposure on AD. The included studies demonstrated considerable spatial and temporal variation. Of the 54 studies, 26 reported a positive association between Al exposure and AD or dementia, while 24 found no or negative associations. Major exposure sources included contaminated water, soil, diet, occupational settings, and medical interventions. Although few studies confirmed Al-induced brain pathology as a direct cause of dementia, meta-analysis of four eligible studies revealed a strong association between Al exposure and AD (Hedges' g = 2.451), despite high heterogeneity across data sources and outcome measures. Our findings suggest that environmental Al exposure may contribute to the development of AD, though it is likely one of several interacting risk factors. Environmental conditions appear to influence both Al bioaccumulation and its neurotoxic effects related to cognitive decline.