{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:36:28Z","timestamp":1792265788019,"version":"4.4.0"},"reference-count":123,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Environmental Health Sciences of the National Institutes of Health (NIH)","award":["R01ES032149"],"award-info":[{"award-number":["R01ES032149"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Emerging evidence suggests a potential link between heavy metals and Alzheimer\u2019s disease and related dementias (AD\/ADRD). This study compiled epidemiological evidence from research published over the past 11 years on the impact of metals on AD\/ADRD in women. Women have unique risk factors for late onset of AD\/ADRD, in addition to genetic factors, apolipoprotein E allele (APOE4), and longer life expectancy. Furthermore, women are twice likely as men to experience depression, which increases their risk of developing AD\/ADRD. Our narrative review underscored the necessity of a sex-specific approach to address women\u2019s vulnerability to AD\/ADRD. Methods: Electronic databases, including PubMed, Google Scholar, NIOSH Toxline, and Scopus, were thoroughly searched to identify primary epidemiological studies on older women exposed to metals and published between 2014 to 2024. Results: We identified 34 epidemiological studies that met the inclusion criteria. The findings revealed a complex interplay between environmental metals such as lead (Pb), cadmium (Cd), arsenic (As), manganese (Mn), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), magnesium (Mg), and calcium (Ca) and the risk of AD\/ADRD in women. Significant adverse effects were reported for Cu, Cd, As, Pb, and Mn while significant protective effects were found between Se, Fe, and Zn in blood and AD\/ADRD among older women. However, some studies also reported no correlations. Conclusions: Overall, our review identified contrasting results regarding the effects of metals on AD\/ADRD in women. Future studies should collect additional evidence to understanding the effects of heavy metals on AD\/ADRD in women for developing preventive measures.<\/jats:p>","DOI":"10.3390\/jcm14113776","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T06:30:26Z","timestamp":1748413826000},"page":"3776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Epidemiological Evidence on the Associations of Metal Exposure with Alzheimer\u2019s Disease and Related Dementias Among Elderly Women"],"prefix":"10.3390","volume":"14","author":[{"given":"Fahmida","family":"Rashid","sequence":"first","affiliation":[{"name":"Department of Public Health, College of Health Sciences, Sam Houston State University, Texas, TX 77341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid M.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Health Sciences, Sam Houston State University, Texas, TX 77341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samyukthaa","family":"Saiprakash","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Sam Houston State University, Texas, TX 77304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giasuddin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biology and Chemistry, Texas A & M International University, Laredo, TX 78041, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-9807","authenticated-orcid":false,"given":"Rasheda","family":"Sultana","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Health Sciences, Sam Houston State University, Texas, TX 77341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faruque","family":"Parvez","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhahirul","family":"Islam","sequence":"additional","affiliation":[{"name":"Gut-Brain Axis Laboratory, Infectious Diseases Division (IDD), Bangladesh (icddr,b), Dhaka 1212, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-4809","authenticated-orcid":false,"given":"Md. Shiblur","family":"Rahaman","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Health Sciences, Sam Houston State University, Texas, TX 77341, USA"},{"name":"Department of Environmental Science and Disaster Management, Noakhali Science and Technology University, Noakhali 3814, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ahmed, G., Rahaman, M.S., Perez, E., and Khan, K.M. (2025). Associations of Environmental Exposure to Arsenic, Manganese, Lead, and Cadmium with Alzheimer\u2019s Disease: A Review of Recent Evidence from Mechanistic Studies. J. Xenobiot., 15.","DOI":"10.20944\/preprints202501.2241.v1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1001\/jamaneurol.2017.0403","article-title":"Dementia care, women\u2019s health, and gender equity: The value of well-timed caregiver support","volume":"74","author":"Bott","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_4","unstructured":"Alzheimer\u2019s Research UK (2025, March 10). Prevalence and Incidence of Dementia. Available online: https:\/\/www.dementiastatistics.org\/about-dementia\/prevalence-and-incidence\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/13607863.2018.1544213","article-title":"WHO\u2019s global action plan on the public health response to dementia: Some challenges and opportunities","volume":"24","author":"Cahill","year":"2020","journal-title":"Aging Ment. Health"},{"key":"ref_6","unstructured":"Prince, M., Albanese, E., Guerchet, M., and Prina, M. (2014). World Alzheimer Report 2014. Dementia and Risk Reduction: An Analysis of Protective and Modifiable Risk Factors, Alzheimer\u2019s Disease International."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(05)67889-0","article-title":"Global prevalence of dementia: A Delphi consensus study","volume":"366","author":"Ferri","year":"2005","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1080\/13607863.2025.2462110","article-title":"Caregiver burden among dementia caregivers in low-and middle-income countries in Asia: A systematic review","volume":"29","author":"Tran","year":"2025","journal-title":"Aging Ment. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13195-023-01244-3","article-title":"Shared genetic risk loci between Alzheimer\u2019s disease and related dementias, Parkinson\u2019s disease, and amyotrophic lateral sclerosis","volume":"15","author":"Wainberg","year":"2023","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.3233\/JAD-200282","article-title":"Heavy metals exposure and Alzheimer\u2019s disease and related dementias","volume":"76","author":"Bakulski","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, H.-X., MacDonald, S.W., Dekhtyar, S., and Fratiglioni, L. (2017). Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study. PLoS Med., 14.","DOI":"10.1371\/journal.pmed.1002251"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e043456","DOI":"10.1136\/bmjopen-2020-043456","article-title":"Outdoor green space exposure and brain health measures related to Alzheimer\u2019s disease: A rapid review","volume":"11","author":"Besser","year":"2021","journal-title":"BMJ Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6754","DOI":"10.1038\/s41467-021-27049-2","article-title":"A national cohort study (2000\u20132018) of long-term air pollution exposure and incident dementia in older adults in the United States","volume":"12","author":"Shi","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Adani, G., Filippini, T., Garuti, C., Malavolti, M., Vinceti, G., Zamboni, G., Tondelli, M., Galli, C., Costa, M., and Vinceti, M. (2020). Environmental risk factors for early-onset Alzheimer\u2019s dementia and frontotemporal dementia: A case-control study in northern Italy. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17217941"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"144072","DOI":"10.1016\/j.scitotenv.2020.144072","article-title":"Higher blood cadmium level is associated with greater cognitive decline in rural Chinese adults aged 65 or older","volume":"756","author":"Liu","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117152","DOI":"10.1016\/j.ecoenv.2024.117152","article-title":"The impact of metals on cognitive impairment in the elderly and the mediating role of oxidative stress: A cross-sectional study in Shanghai, China","volume":"286","author":"Qing","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.envres.2013.12.010","article-title":"Lead exposure and rate of change in cognitive function in older women","volume":"129","author":"Power","year":"2014","journal-title":"Environ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1007\/s12011-021-02941-6","article-title":"Associations between plasma metals and cognitive function in people aged 60 and above","volume":"200","author":"Zhang","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neuro.2020.11.009","article-title":"Association of arsenic exposure and cognitive impairment: A population-based cross-sectional study in China","volume":"82","author":"Wang","year":"2021","journal-title":"Neurotoxicology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2017). 2017 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 13, 325\u2013373.","DOI":"10.1016\/j.jalz.2017.02.001"},{"key":"ref_21","first-page":"14","article-title":"Sex and gender differences in Alzheimer\u2019s disease dementia","volume":"35","author":"Mielke","year":"2018","journal-title":"Psychiatr. Times"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000109998","article-title":"Prevalence of dementia in the United States: The aging, demographics, and memory study","volume":"29","author":"Plassman","year":"2007","journal-title":"Neuroepidemiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.3233\/JAD-180141","article-title":"Differences between women and men in incidence rates of dementia and Alzheimer\u2019s disease","volume":"64","author":"Beam","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1212\/WNL.0000000000004602","article-title":"Female sex, early-onset hypertension, and risk of dementia","volume":"89","author":"Gilsanz","year":"2017","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0165-0327(93)90026-G","article-title":"Sex and depression in the National Comorbidity Survey I: Lifetime prevalence, chronicity and recurrence","volume":"29","author":"Kessler","year":"1993","journal-title":"J. Affect. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1532-5415.2010.03233.x","article-title":"Depressive symptoms and incidence of mild cognitive impairment and probable dementia in elderly women: The Women\u2019s Health Initiative Memory Study","volume":"59","author":"Goveas","year":"2011","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/aje\/kwh018","article-title":"Relation of education and occupation-based socioeconomic status to incident Alzheimer\u2019s disease","volume":"159","author":"Karp","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1192\/bjp.bp.112.119479","article-title":"Socioeconomic status as a risk factor for dementia death: Individual participant meta-analysis of 86 508 men and women from the UK","volume":"203","author":"Russ","year":"2013","journal-title":"Br. J. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.brainres.2010.10.031","article-title":"Oophorectomy, menopause, estrogen treatment, and cognitive aging: Clinical evidence for a window of opportunity","volume":"1379","author":"Rocca","year":"2011","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mishra, S., Singh, G., Gupta, A., and Tiwari, R.K. (2023). Heavy metal\/metalloid contamination: Their sources in environment and accumulation in food chain. Heavy Metal Toxicity: Environmental Concerns, Remediation and Opportunities, Springer.","DOI":"10.1007\/978-981-99-0397-9_2"},{"key":"ref_31","first-page":"S345","article-title":"Metabolites and cognitive decline in a Puerto Rican cohort","volume":"99","author":"Gordon","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1007\/s11033-021-06386-x","article-title":"Metals toxicity and its correlation with the gene expression in Alzheimer\u2019s disease","volume":"48","author":"Yadav","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.taap.2018.07.015","article-title":"Risk of Alzheimer\u2019s disease with metal concentrations in whole blood and urine: A case\u2013control study using propensity score matching","volume":"356","author":"Yang","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gong, Z., Song, W., Gu, M., Zhou, X., and Tian, C. (2021). Association between serum iron concentrations and cognitive impairment in older adults aged 60 years and older: A dose-response analysis of National Health and Nutrition Examination Survey. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255595"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e20200984","DOI":"10.1590\/0034-7167-2020-0984","article-title":"Selenium concentrations in elderly people with Alzheimer\u2019s disease: A cross-sectional study with control group","volume":"74","author":"Nascimento","year":"2021","journal-title":"Rev. Bras. Enferm."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Socha, K., Klimiuk, K., Naliwajko, S.K., Soroczy\u0144ska, J., Pu\u015bcion-Jakubik, A., Markiewicz-\u017bukowska, R., and Kochanowicz, J. (2021). Dietary habits, selenium, copper, zinc and total antioxidant status in serum in relation to cognitive functions of patients with Alzheimer\u2019s disease. Nutrients, 13.","DOI":"10.3390\/nu13020287"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sukumaran, P., Nascimento Da Conceicao, V., Sun, Y., Ahamad, N., Saraiva, L.R., Selvaraj, S., and Singh, B.B. (2021). Calcium signaling regulates autophagy and apoptosis. Cells, 10.","DOI":"10.3390\/cells10082125"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1177\/1533317518794032","article-title":"Comparison of blood lead levels in patients with Alzheimer\u2019s disease and healthy people","volume":"33","author":"Fathabadi","year":"2018","journal-title":"Am. J. Alzheimer\u2019s Dis. Other Dement."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Botturi, A., Ciappolino, V., Delvecchio, G., Boscutti, A., Viscardi, B., and Brambilla, P. (2020). The role and the effect of magnesium in mental disorders: A systematic review. Nutrients, 12.","DOI":"10.3390\/nu12061661"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.neuro.2017.09.012","article-title":"Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles","volume":"64","author":"Kornblith","year":"2018","journal-title":"Neurotoxicology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1039\/C7MT00079K","article-title":"Influence of iron metabolism on manganese transport and toxicity","volume":"9","author":"Ye","year":"2017","journal-title":"Metallomics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3109\/00365513.2014.936694","article-title":"Iron deficiency and iron deficiency anemia in women","volume":"74","author":"Coad","year":"2014","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1210\/en.2011-2045","article-title":"17\u03b2-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site","volume":"153","author":"Yang","year":"2012","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"119148","DOI":"10.1016\/j.envres.2024.119148","article-title":"APOE \u03b54 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults","volume":"255","author":"Liu","year":"2024","journal-title":"Environ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fu, Z., Xu, X., Cao, L., Xiang, Q., Gao, Q., Duan, H., Wang, S., Zhou, L., and Yang, X. (2024). Single and joint exposure of Pb, Cd, Hg, Se, Cu, and Zn were associated with cognitive function of older adults. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-79720-5"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ashraf, A., Stosnach, H., Parkes, H.G., Hye, A., Powell, J., and So, P.-W. (2019). Pattern of altered plasma elemental phosphorus, calcium, zinc, and iron in Alzheimer\u2019s disease. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37431-8"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jtemb.2019.06.001","article-title":"Acetylcholinesterase inhibitors in Alzheimer\u2019s disease influence Zinc and Copper homeostasis","volume":"55","author":"Giacconi","year":"2019","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1039\/C4MT00060A","article-title":"Decreased serum zinc is an effect of ageing and not Alzheimer\u2019s disease","volume":"6","author":"Rembach","year":"2014","journal-title":"Metallomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12011-022-03136-3","article-title":"Associations between mild cognitive impairment and whole blood zinc and selenium in the elderly cohort","volume":"201","author":"Yu","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12940-016-0155-7","article-title":"Blood cadmium levels and Alzheimer\u2019s disease mortality risk in older US adults","volume":"15","author":"Min","year":"2016","journal-title":"Environ. Health"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.envres.2017.05.011","article-title":"Cadmium and Alzheimer\u2019s disease mortality in US adults: Updated evidence with a urinary biomarker and extended follow-up time","volume":"157","author":"Peng","year":"2017","journal-title":"Environ. Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Koseoglu, E., Kutuk, B., Nalbantoglu, O.U., Koseoglu, R., and Kendirci, M. (2021). Arsenic and selenium measurements in nail and hair show important relationships to Alzheimer\u2019s disease in the elderly. J. Trace Elem. Med. Biol., 64.","DOI":"10.1016\/j.jtemb.2020.126684"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3233\/JAD-160622","article-title":"Selenium levels in serum, red blood cells, and cerebrospinal fluid of Alzheimer\u2019s disease patients: A report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL)","volume":"57","author":"Cardoso","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s12011-020-02154-3","article-title":"The association between trace elements exposure and the cognition in the elderly in China","volume":"199","author":"Gu","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Huang, G., and Ren, G. (2022). Interaction between \u03c9-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011\u20132014. BMC Geriatr., 22.","DOI":"10.1186\/s12877-022-02988-7"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.3233\/JAD-201250","article-title":"Impacts of iron metabolism dysregulation on Alzheimer\u2019s disease","volume":"80","author":"Jouini","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.3906\/sag-1407-67","article-title":"A comparison of hair and serum trace elements in patients with Alzheimer disease and healthy participants","volume":"45","author":"Ilhan","year":"2015","journal-title":"Turk. J. Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e020533","DOI":"10.1136\/bmjopen-2017-020533","article-title":"Associations between blood cadmium levels and cognitive function in a cross-sectional study of US adults aged 60 years or older","volume":"8","author":"Li","year":"2018","journal-title":"BMJ Open"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00234-019-02159-3","article-title":"Motor cortex hypointensity on susceptibility-weighted imaging: A potential imaging marker of iron accumulation in patients with cognitive impairment","volume":"61","author":"Park","year":"2019","journal-title":"Neuroradiology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3233\/JAD-170552","article-title":"Serum non-ceruloplasmin non-albumin copper elevation in mild cognitive impairment and dementia due to Alzheimer\u2019s disease: A case control study","volume":"61","author":"Rozzini","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"215","DOI":"10.14336\/AD.2016.0811","article-title":"Serum hepcidin levels, iron dyshomeostasis and cognitive loss in Alzheimer\u2019s disease","volume":"8","author":"Sternberg","year":"2017","journal-title":"Aging Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s10534-018-0089-3","article-title":"Plasma metals as potential biomarkers in dementia: A case\u2013control study in patients with sporadic Alzheimer\u2019s disease","volume":"31","author":"Xu","year":"2018","journal-title":"Biometals"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"113182","DOI":"10.1016\/j.ecoenv.2022.113182","article-title":"The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults","volume":"231","author":"Cheng","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1007\/s12011-023-03774-1","article-title":"Multi-element Exposure and Cognitive Function in Rural Elderly Chinese","volume":"202","author":"Duan","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1039\/C6MT00019C","article-title":"Lead and manganese levels in serum and erythrocytes in Alzheimer\u2019s disease and mild cognitive impairment: Results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing","volume":"8","author":"Hare","year":"2016","journal-title":"Metallomics"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wang, N., Guo, L., Shi, M., Wang, L., Zhou, Y., Liu, H., and Xu, X.Q. (2024). Association of single and combined effects of blood heavy metals with cognitive function in older adults of the United States: A cross-sectional study. Res. Sq.","DOI":"10.21203\/rs.3.rs-4786268\/v1"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, X., Wang, B., Yang, F., Shang, K., Chen, S., and Zhang, Y. (2024). Associations between plasma metal elements and risk of cognitive impairment among Chinese older adults. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1353286"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Torres-Rojas, C., and Jones, B.C. (2018). Sex differences in neurotoxicogenetics. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00196"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12011-018-1492-x","article-title":"Brain selenium in Alzheimer\u2019s disease (BRAIN SEAD Study): A systematic review and meta-analysis","volume":"189","author":"Varikasuvu","year":"2019","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00204-024-03903-2","article-title":"Heavy metals: Toxicity and human health effects","volume":"99","author":"Jomova","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1017\/S1355617707071020","article-title":"The Indiana University telephone-based assessment of neuropsychological status: A new method for large scale neuropsychological assessment","volume":"13","author":"Unverzagt","year":"2007","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1097\/EDE.0b013e3181b5f100","article-title":"Cumulative lead dose and cognitive function in older adults","volume":"20","author":"Glass","year":"2009","journal-title":"Epidemiology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/01.ede.0000248237.35363.29","article-title":"Cumulative lead exposure and cognitive performance among elderly men","volume":"18","author":"Weisskopf","year":"2007","journal-title":"Epidemiology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1037\/a0013757","article-title":"Association of cumulative lead and neurocognitive function in an occupational cohort","volume":"23","author":"Khalil","year":"2009","journal-title":"Neuropsychology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Deng, Y., Lin, X., Zhou, J., Li, M., Fu, Z., and Song, D. (2023). Concurrent serum lead levels and cognitive function in older adults. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1180782"},{"key":"ref_76","first-page":"231","article-title":"Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer\u2019s disease","volume":"3","author":"Basun","year":"1991","journal-title":"J. Neural Transm. Park. Dis. Dement. Sect."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1532-5415.1990.tb01421.x","article-title":"Metals and the Liver in Alzheimer\u2019s Disease An Investigation of Hepatic Zinc, Copper, Cadmium, and Metallothionein","volume":"38","author":"Lui","year":"1990","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-510X(01)00672-4","article-title":"Determination of cadmium and zinc in Alzheimer\u2019s brain tissue using inductively coupled plasma mass spectrometry","volume":"195","author":"Panayi","year":"2002","journal-title":"J. Neurol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"M\u0119cik-Kronenberg, T., Ku\u0107, A., Kubik-Machura, D., Ko\u015bcielecka, K., and Radko, L. (2023). Interaction of Metals, Menopause and COVID-19\u2014A Review of the Literature. Biology, 12.","DOI":"10.3390\/biology12030350"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.envres.2017.01.028","article-title":"Low-level arsenic in drinking water and risk of incident myocardial infarction: A cohort study","volume":"154","author":"Monrad","year":"2017","journal-title":"Environ. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s10522-009-9251-1","article-title":"Plasma copper\/zinc ratio: An inflammatory\/nutritional biomarker as predictor of all-cause mortality in elderly population","volume":"11","author":"Malavolta","year":"2010","journal-title":"Biogerontology"},{"key":"ref_82","first-page":"0495","article-title":"Copper and zinc, biological role and significance of copper\/zinc imbalance","volume":"3","author":"Osredkar","year":"2011","journal-title":"J. Clin. Toxicol. S"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Burmistrov, D.E., Gudkov, S.V., Franceschi, C., and Vedunova, M.V. (2024). Sex as a determinant of age-related changes in the brain. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137122"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Pinares-Garcia, P., Stratikopoulos, M., Zagato, A., Loke, H., and Lee, J. (2018). Sex: A significant risk factor for neurodevelopmental and neurodegenerative disorders. Brain Sci., 8.","DOI":"10.3390\/brainsci8080154"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.yfrne.2007.08.002","article-title":"Brain aging modulates the neuroprotective effects of estrogen on selective aspects of cognition in women: A critical review","volume":"29","author":"Sherwin","year":"2008","journal-title":"Front. Neuroendocrinol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0306-4530(91)90017-N","article-title":"Cerebrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood-brain barrier function in primary hyperparathyroidism","volume":"16","author":"Joborn","year":"1991","journal-title":"Psychoneuroendocrinology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0070-2153(05)73003-9","article-title":"Calcium sensing receptors and calcium oscillations: Calcium as a first messenger","volume":"73","author":"Breitwieser","year":"2006","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_88","unstructured":"Tsien, R.W., and Wheeler, D.B. (1999). Voltage-gated calcium channels. Calcium as a Cellular Regulator, Oxford University Press."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0143-4160(02)00054-4","article-title":"Calcium influx constitutes the ionic basis for the maintenance of glutamate-induced extended neuronal depolarization associated with hippocampal neuronal death","volume":"33","author":"Sombati","year":"2003","journal-title":"Cell Calcium"},{"key":"ref_90","first-page":"1176","article-title":"Normal and abnormal calcium homeostasis in neurons: A basis for the pathophysiology of traumatic and ischemic central nervous system injury","volume":"38","author":"Tymianski","year":"1996","journal-title":"Neurosurgery"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.nutres.2019.09.008","article-title":"Severe calcium deficiency increased visceral fat accumulation, down-regulating genes associated with fat oxidation, and increased insulin resistance while elevating serum parathyroid hormone in estrogen-deficient rats","volume":"73","author":"Park","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.neurobiolaging.2012.06.018","article-title":"Neural activities during affective processing in people with Alzheimer\u2019s disease","volume":"34","author":"Lee","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"114011","DOI":"10.1016\/j.envpol.2020.114011","article-title":"Toxicogenomics provides insights to toxicity pathways of neonicotinoids to aquatic insect, Chironomus dilutus","volume":"260","author":"Wei","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3233\/JAD-151037","article-title":"Patterns of brain iron accumulation in vascular dementia and Alzheimer\u2019s dementia using quantitative susceptibility mapping imaging","volume":"51","author":"Moon","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Park, M., Moon, W.-J., Moon, Y., Choi, J.W., Han, S.-H., and Wang, Y. (2018). Region-specific susceptibility change in cognitively impaired patients with diabetes mellitus. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205797"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S1474-4422(14)70117-6","article-title":"The role of iron in brain ageing and neurodegenerative disorders","volume":"13","author":"Ward","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev-nutr-071812-161205","article-title":"Iron nutrition and premenopausal women: Effects of poor iron status on physical and neuropsychological performance","volume":"33","author":"McClung","year":"2013","journal-title":"Annu. Rev. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3233\/JAD-191183","article-title":"Sex differences in in vivo Alzheimer\u2019s disease neuropathology in late middle-aged Hispanics","volume":"74","author":"Luchsinger","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.arr.2016.09.005","article-title":"Sex differences in the prevalence and incidence of mild cognitive impairment: A meta-analysis","volume":"35","author":"Au","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"S513","DOI":"10.1111\/jgs.15728","article-title":"Sex differences in the prevalence and incidence of cognitive impairment: Does immigration matter?","volume":"67","author":"Tang","year":"2019","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1158\/1535-7163.MCT-13-0896","article-title":"SGN\u2013LIV1A: A novel antibody\u2013drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer","volume":"13","author":"Sussman","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jtemb.2014.08.009","article-title":"Selenium status in elderly: Relation to cognitive decline","volume":"28","author":"Cardoso","year":"2014","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1017\/S0007114509992832","article-title":"Nutritional status of selenium in Alzheimer\u2019s disease patients","volume":"103","author":"Cardoso","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jtemb.2010.02.002","article-title":"Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer\u2019s disease","volume":"24","author":"Vural","year":"2010","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/aje\/kwad082","article-title":"Metal exposure and risk of Parkinson disease: A systematic review and meta-analysis","volume":"192","author":"Zhao","year":"2023","journal-title":"Am. J. Epidemiol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Baj, J., Flieger, W., Barbachowska, A., Kowalska, B., Flieger, M., Forma, A., Teresi\u0144ski, G., Portincasa, P., Buszewicz, G., and Radzikowska-B\u00fcchner, E. (2023). Consequences of disturbing manganese homeostasis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914959"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Antonioni, A., Govoni, V., Brancaleoni, L., Don\u00e0, A., Granieri, E., Bergamini, M., Gerdol, R., and Pugliatti, M. (2023). Amyotrophic lateral sclerosis and air pollutants in the province of Ferrara, Northern Italy: An ecological study. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20085591"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/00001648-200205000-00012","article-title":"Lead exposure and amyotrophic lateral sclerosis","volume":"13","author":"Kamel","year":"2002","journal-title":"Epidemiology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e2448286","DOI":"10.1001\/jamanetworkopen.2024.48286","article-title":"Urinary metal levels, cognitive test performance, and dementia in the Multi-Ethnic Study of Atherosclerosis","volume":"7","author":"McGraw","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuron.2018.06.030","article-title":"Alzheimer\u2019s disease-associated \u03b2-amyloid is rapidly seeded by herpesviridae to protect against brain infection","volume":"99","author":"Eimer","year":"2018","journal-title":"Neuron"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nrcardio.2016.45","article-title":"Atrial fibrillation in women: Epidemiology, pathophysiology, presentation, and prognosis","volume":"13","author":"Ko","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1111\/j.1532-5415.2007.01308.x","article-title":"Oxidative stress is associated with greater mortality in older women living in the community","volume":"55","author":"Semba","year":"2007","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.etap.2016.09.016","article-title":"Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain","volume":"48","author":"Karri","year":"2016","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Z\u00e1rate, S., Stevnsner, T., and Gredilla, R. (2017). Role of estrogen and other sex hormones in brain aging. Neuroprotection and DNA repair. Front. Aging Neurosci., 9.","DOI":"10.3389\/fnagi.2017.00430"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Mehta, S.W., and Eikum, R. (1989). Effect of estrogen on serum and tissue levels of copper and zinc. Copper Bioavailability and Metabolism, Springer.","DOI":"10.1007\/978-1-4613-0537-8_13"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Dacks, P.A. (2012). Estrogens Iron out the Details: A Novel Direct Pathway for Estrogen Control of Iron Homeostasis, Oxford University Press.","DOI":"10.1210\/en.2012-1480"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jnutbio.2011.02.008","article-title":"Estrogen status alters tissue distribution and metabolism of selenium in female rats","volume":"23","author":"Zhou","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1177\/153537020422900506","article-title":"Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction","volume":"229","author":"Henson","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/toxsci\/kfp081","article-title":"Estrogen and tamoxifen protect against Mn-induced toxicity in rat cortical primary cultures of neurons and astrocytes","volume":"110","author":"Lee","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.0959-9673.2005.00434.x","article-title":"Metals and amyloid-\u03b2 in Alzheimer\u2019s disease","volume":"86","author":"Maynard","year":"2005","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Sun, R., Wang, J., Feng, J., and Cao, B. (2022). Zinc in cognitive impairment and aging. Biomolecules, 12.","DOI":"10.3390\/biom12071000"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Zhou, J., Zhang, W., Cao, Z., Lian, S., Li, J., Nie, J., Huang, Y., Zhao, K., He, J., and Liu, C. (2023). Association of selenium levels with neurodegenerative disease: A systemic review and meta-analysis. Nutrients, 15.","DOI":"10.21203\/rs.3.rs-2584949\/v1"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Vural, Z., Avery, A., Kalogiros, D.I., Coneyworth, L.J., and Welham, S.J. (2020). Trace mineral intake and deficiencies in older adults living in the community and institutions: A systematic review. Nutrients, 12.","DOI":"10.3390\/nu12041072"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:42:02Z","timestamp":1760031722000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/11\/3776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":123,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["jcm14113776"],"URL":"https:\/\/doi.org\/10.3390\/jcm14113776","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,28]]}}}