{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:52:09Z","timestamp":1791611529626,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cPRIN 2022 PNRR\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["P20229KSXB"],"award-info":[{"award-number":["P20229KSXB"]}]},{"name":"\u201cPRIN 2022 PNRR\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["UNIMORE FAR 2023"],"award-info":[{"award-number":["UNIMORE FAR 2023"]}]},{"name":"\u201cPRIN 2022 PNRR\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["2022MHMRPR"],"award-info":[{"award-number":["2022MHMRPR"]}]},{"name":"\u201cPRIN 2022 PNRR\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["101042625"],"award-info":[{"award-number":["101042625"]}]},{"name":"University of Modena and Reggio Emilia","award":["P20229KSXB"],"award-info":[{"award-number":["P20229KSXB"]}]},{"name":"University of Modena and Reggio Emilia","award":["UNIMORE FAR 2023"],"award-info":[{"award-number":["UNIMORE FAR 2023"]}]},{"name":"University of Modena and Reggio Emilia","award":["2022MHMRPR"],"award-info":[{"award-number":["2022MHMRPR"]}]},{"name":"University of Modena and Reggio Emilia","award":["101042625"],"award-info":[{"award-number":["101042625"]}]},{"name":"\u201cPRIN 2022\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["P20229KSXB"],"award-info":[{"award-number":["P20229KSXB"]}]},{"name":"\u201cPRIN 2022\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["UNIMORE FAR 2023"],"award-info":[{"award-number":["UNIMORE FAR 2023"]}]},{"name":"\u201cPRIN 2022\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["2022MHMRPR"],"award-info":[{"award-number":["2022MHMRPR"]}]},{"name":"\u201cPRIN 2022\u201d from the Italian Ministry of University and Research (MUR) funded by European Union\u2014Next Generation EU","award":["101042625"],"award-info":[{"award-number":["101042625"]}]},{"name":"ERC (UnaWireD, ERC-2021-STG)","award":["P20229KSXB"],"award-info":[{"award-number":["P20229KSXB"]}]},{"name":"ERC (UnaWireD, ERC-2021-STG)","award":["UNIMORE FAR 2023"],"award-info":[{"award-number":["UNIMORE FAR 2023"]}]},{"name":"ERC (UnaWireD, ERC-2021-STG)","award":["2022MHMRPR"],"award-info":[{"award-number":["2022MHMRPR"]}]},{"name":"ERC (UnaWireD, ERC-2021-STG)","award":["101042625"],"award-info":[{"award-number":["101042625"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: A limited number of studies have investigated the role of environmental chemicals in the etiology of mild cognitive impairment (MCI). We performed a cross-sectional study of the association between exposure to selected trace elements and the biomarkers of cognitive decline. Methods: During 2019\u20132021, we recruited 128 newly diagnosed patients with MCI from two Neurology Clinics in Northern Italy, i.e., Modena and Reggio Emilia. At baseline, we measured serum and cerebrospinal fluid (CSF) concentrations of cadmium, copper, iron, manganese, and zinc using inductively coupled plasma mass spectrometry. With immuno-enzymatic assays, we estimated concentrations of \u03b2-amyloid 1-40, \u03b2-amyloid 1-42, Total Tau and phosphorylated Tau181 proteins, neurofilament light chain (NfL), and the mini-mental state examination (MMSE) to assess cognitive status. We used spline regression to explore the shape of the association between exposure and each endpoint, adjusted for age at diagnosis, educational attainment, MMSE, and sex. Results: In analyses between the serum and CSF concentrations of trace metals, we found monotonic positive correlations between copper and zinc, while an inverse association was observed for cadmium. Serum cadmium concentrations were inversely associated with amyloid ratio and positively associated with Tau proteins. Serum iron concentrations showed the opposite trend, while copper, manganese, and zinc displayed heterogeneous non-linear associations with amyloid ratio and Tau biomarkers. Regarding CSF exposure biomarkers, only cadmium consistently showed an inverse association with amyloid ratio, while iron was positively associated with Tau. Cadmium concentrations in CSF were not appreciably associated with serum NfL levels, while we observed an inverted U-shaped association with CSF NfL, similar to that observed for copper. In CSF, zinc was the only trace element positively associated with NfL at high concentrations. Conclusions: In this cross-sectional study, high serum cadmium concentrations were associated with selected biomarkers of cognitive impairment. Findings for the other trace elements were difficult to interpret, showing complex and inconsistent associations with the neurodegenerative endpoints examined.<\/jats:p>","DOI":"10.3390\/toxics12120933","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T04:45:49Z","timestamp":1735015549000},"page":"933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Exposure to Cadmium and Other Trace Elements Among Individuals with Mild Cognitive Impairment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-5508","authenticated-orcid":false,"given":"Teresa","family":"Urbano","sequence":"first","affiliation":[{"name":"Environmental, Genetics, and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-2473","authenticated-orcid":false,"given":"Marco","family":"Vinceti","sequence":"additional","affiliation":[{"name":"Environmental, Genetics, and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Neurology Unit, Baggiovara Hospital, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-3752","authenticated-orcid":false,"given":"Lauren A.","family":"Wise","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Malavolti","sequence":"additional","affiliation":[{"name":"Environmental, Genetics, and Nutritional Epidemiology Research Center (CREAGEN), Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6698-5437","authenticated-orcid":false,"given":"Manuela","family":"Tondelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Neurology Unit, Baggiovara Hospital, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5006-3294","authenticated-orcid":false,"given":"Roberta","family":"Bedin","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1055-8908","authenticated-orcid":false,"given":"Giulia","family":"Vinceti","sequence":"additional","affiliation":[{"name":"Neurology Unit, Baggiovara Hospital, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Marti","sequence":"additional","affiliation":[{"name":"Clinical Neuropsychology, Cognitive Disorders and Dyslexia Unit, Neuromotor and Rehabilitation Department, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Chiari","sequence":"additional","affiliation":[{"name":"Neurology Unit, Baggiovara Hospital, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Neurology Unit, Baggiovara Hospital, 41126 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Michalke","sequence":"additional","affiliation":[{"name":"Research Unit Analytical BioGeoChemistry, German Research Center for Environmental Health, Helmholtz Center Munich, 85764 Neuherberg, 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