{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:55:12Z","timestamp":1790848512684,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["GAP\u2010398"],"award-info":[{"award-number":["GAP\u2010398"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["GAP 398"],"award-info":[{"award-number":["GAP 398"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heavy metal exposure has been associated with dementia, though findings remain inconsistent and without stage\u2010specific insight. We conducted a systematic review and meta\u2010analyses of heavy metal levels in blood and serum to assess them across severities in dementia patients. Searches of Google Scholar, PubMed, and Cochrane Library (1954\u20132023) identified six studies, including 598 dementia patients and 622 controls. Thirteen metals were analyzed, with emphasis on lead, cadmium, copper, and mercury, most consistently reported across studies. Cognitive performance, which declines with increasing dementia severity, was measured using MMSE and MoCA scores. Pooled standardized mean differences (SMDs) were calculated mainly with random effects models. The dementia patients, overall, had significantly higher heavy metal levels in blood or serum than controls (SMD\u2009=\u20090.499,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.000). Stage\u2010specific analyses showed no significant differences in mild dementia but marked increases in moderate\u2010to\u2010severe (SMD\u2009=\u20090.617,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.000), primarily driven by cadmium (SMD\u2009=\u20090.838,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.019) and copper (SMD\u2009=\u20092.202,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). Correlation analyses demonstrated that pooled heavy metals had a strong positive relationship with cognitive scores in mild dementia (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.818,\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.670,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001), while weaker and varied associations were noted in overall and moderate\u2010to\u2010severe stages. Despite heterogeneity, sensitivity analyses reinforced the stability of results. This study provides novel stage\u2010specific meta\u2010analytical evidence that heavy metals act as accelerators rather than initiators of dementia. Cadmium and copper are significant contributors to advanced neurodegeneration, emphasizing the need for standardized assessments and targeted interventions to address environmental risks.\n                  <\/jats:p>","DOI":"10.1002\/jat.70130","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:46:48Z","timestamp":1773103608000},"page":"3837-3857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heavy Metals as Accelerators of Dementia Progression: Evidence From a Stage\u2010Specific Systematic Review and Meta\u2010Analyses"],"prefix":"10.1002","volume":"46","author":[{"given":"Asmita","family":"Garg","sequence":"first","affiliation":[{"name":"Systems Toxicology Group, Food, Drug &amp; Chemical, Environment and Systems Toxicology Division CSIR\u2010Indian Institute of Toxicology Research (CSIR\u2010IITR)  Lucknow Uttar Pradesh India"},{"name":"Academy of Scientific and 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