Association between metal(loid)s in different biospecimens and dementia: A systematic review and meta-analysis

Metal (loid)s are widely present in the environment and affect human health, especially the central nervous system. Dementia is a syndrome characterized by cognitive decline that can be caused by neurological degeneration. We aimed to review the current state of knowledge with respect to associations between various metal(loid)s in different biospecimens and dementia. We searched PubMed, Embase, and Web of Science for original research in English up to January 15th, 2025. We evaluated the synthesized using random effects and cumulative meta-analysis and assessed the risk of bias using the Newcastle-Ottawa Scale tool and the certainty of evidence by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Of the 7390 publications identified, 82 articles met the eligibility criteria. In the present meta-analysis, hair iron, serum zinc, cerebrospinal fluid zinc, and blood selenium showed significant negative associations with dementia. Urine iron, serum lead, and serum aluminum were significantly positively associated with dementia. It may be hypothesized that zinc/selenium/iron deficiency was the pathogenic factor for the onset or development of dementia. Increasing serum lead/aluminum may lead to dementia, especially in lower economic level countries. Because of the high heterogeneity, methodological limitations, and quality of evidence, the present findings should be interpreted with caution. The review was prospectively registered on PROSPERO CRD42024502024.