PMID- 38494026 OWN - NLM STAT- MEDLINE DCOM- 20240401 LR - 20240401 IS - 1879-1026 (Electronic) IS - 0048-9697 (Linking) VI - 925 DP - 2024 May 15 TI - Sex and age disparities in multi-metal mixture exposure and cognitive impairment in urban elderly individuals: The mediation effect and biological function of metabolites. PG - 171736 LID - S0048-9697(24)01879-5 [pii] LID - 10.1016/j.scitotenv.2024.171736 [doi] AB - Studies on the relationships between metal mixtures exposure and cognitive impairment in elderly individuals are limited, particularly the mechanism with metabolite. Few studies are available on the potential sex and age specific associations between metal exposure, metabolites and cognitive impairment. We examined plasma metal and blood metabolite concentrations among 1068 urban elderly participants. Statistical analysis included a battery of variable selection approaches, logistic regression for metal/metabolite associations, and Bayesian kernel machine regression (BKMR) to identify mixed effects of metals/metabolites on cognitive impairment risk. Our results showed that As was positively associated with cognitive impairment in the female (OR 95 % CI = 2.21 (1.36, 3.57)) and 60- to 70-year-old (OR 95 % CI = 2.60 (1.54, 4.41)) groups, Cr was positively associated with cognitive impairment in the male (OR 95 % CI = 2.15 (1.27, 3.63)) and 60- to 70-year-old (OR 95 % CI = 2.10 (1.24, 3.57)) groups, and Zn was negatively associated with cognitive impairment, especially in the female (OR 95 % CI = 0.46 (0.25, 0.84)), 60- to 70-year-old (OR 95 % CI =0.24 (0.12, 0.45)) and >/= 80-year-old (OR 95 % CI = 0.19 (0.04, 0.86)) groups. Positive associations were observed between combined metals (Cr, Cu and As) and cognitive impairment, but Zn alleviated this tendency, especially in elderly individuals aged >/=80 years. Negative associations were observed between metabolites and cognitive impairment, especially in male, female and 60-70 years old groups. The mediation effects of metabolites on the association between metal exposure and cognitive impairment were observed, and the percentages of these effects were 15.60 % (Glu-Cr), 23.00 % (C5:1-Cu) and 16.36 % (Glu-Zn). Cr, Cu, and Zn could increase cognitive impairment risk through the "Malate-Aspartate Shuttle", "Glucose-Alanine Cycle", etc., pathways. Overall, we hypothesize that metabolites have mediation effects on the relationship between multi-metal exposure and cognitive impairment and that there are sex and age differences. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Hou, Qingzhi AU - Hou Q AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. Electronic address: qzhou@sdfmu.edu.cn. FAU - Lin, Jiujing AU - Lin J AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Xue, Xiangsheng AU - Xue X AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Zhang, Yuchen AU - Zhang Y AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Qiu, Zhanhui AU - Qiu Z AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Zhang, Haoran AU - Zhang H AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Li, Jia AU - Li J AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Wang, Harry AU - Wang H AD - School of Health Sciences, University of Newcastle, University Drive, Callaghan, Newcastle, Australia. FAU - Zhang, Shuping AU - Zhang S AD - Medical Science and Technology Innovation Center, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Yao, Zhigang AU - Yao Z AD - Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Fifth Ring Road and the Seventh Ring Road, Jinan, PR China. FAU - Li, Xiaomei AU - Li X AD - School of public health and management, Shandong First Medical University, Shandong Academy of Medical Sciences, No.6699 Qingdao Road, Huaiyin District, Jinan 250117, PR China. FAU - Wang, Fei AU - Wang F AD - School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Qingxiu District, Nanning 530021, PR China. FAU - Gu, Aihua AU - Gu A AD - State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, No101 Longmian Avenue, Jiangning District, Nanjing 211166, PR China. Electronic address: aihuagu@njmu.edu.cn. FAU - Liu, Yajun AU - Liu Y AD - Beijing Jishuitan Hospital, Capital Medical University, No. 31 Xinjiekou East Road, Xicheng District, Beijing 100035, PR China; Beijing Research Institute of Traumatology and Orthopaedics, No. 31 Xinjiekou East Road, Xicheng District, Beijing 100035, PR China. Electronic address: drliuyajun@163.com. LA - eng PT - Journal Article DEP - 20240316 PL - Netherlands TA - Sci Total Environ JT - The Science of the total environment JID - 0330500 RN - 0 (Metals) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Aged MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged, 80 and over MH - Bayes Theorem MH - *Metals MH - *Glucose OTO - NOTNLM OT - Cognitive impairment OT - Mediator effect OT - Metabolite OT - Multiple metals OT - Sex and age differences OT - Urban elderly COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2024/03/18 00:42 MHDA- 2024/04/01 06:43 CRDT- 2024/03/17 20:29 PHST- 2024/01/18 00:00 [received] PHST- 2024/03/05 00:00 [revised] PHST- 2024/03/13 00:00 [accepted] PHST- 2024/04/01 06:43 [medline] PHST- 2024/03/18 00:42 [pubmed] PHST- 2024/03/17 20:29 [entrez] AID - S0048-9697(24)01879-5 [pii] AID - 10.1016/j.scitotenv.2024.171736 [doi] PST - ppublish SO - Sci Total Environ. 2024 May 15;925:171736. doi: 10.1016/j.scitotenv.2024.171736. Epub 2024 Mar 16.