Correlation between Cadmium and Alzheimer's Disease:A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LIHui ¹ , MAOShao-ju ¹ , SUNWei-xuan ^1,2 , LIAOZhi-lin ^1,3 , TANGHan-mei ¹ , FUYan-yan ¹ ,  HUANGPeng ¹

1. Department of Epidemiology, School of Public Health, Nanchang University, Nanchang 330006, China;
2. Department of Public Health Service, Futian Center for Maternity and Child Care, Shenzhen 518045, China;
3. Department of Emergency, Nanchang 334 Hospital, Nanchang 330001, China;

Corresponding author：

HUANGPeng, Email: huangpengncu@163.com

Keywords：

Alzheimer's disease; Cadmium; Meta-analysis; Case-control study

DOI：

10.7507/1672-2531.20150172

Video：

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Objective To systematically review the relationship between Cadmium (Cd) level and Alzheimer's disease (AD). Method We searched PubMed, EMbase, CNKI, WanFang Data and CBM databases from inception to December 2014 to collect case-control studies about the relationship between Cd level and AD. Two reviewers screened literature, extracted data and evaluated the risk of bias of included studies, and then meta-analysis was performed by using RevMan 5.3 software. Results A total of 11 studies were included, among them 8 studies were included into final meta-analysis. Three studies including 154 patients and 141 controls reported the relationship of serum Cd concentrations and AD, and the result of meta-analysis showed that the higher serum Cd level was found in the AD group than the control group (SMD=0.36, 95%CI 0.12 to 0.59, P=0.003). Six studies including 358 patients and 423 controls reported the relationship of blood Cd concentrations and AD, and the result of meta-analysis showed that there was no significant difference of blood Cd levels between both groups (SMD=0.35, 95%CI -0.14 to 0.84, P=0.16). Conclusion Serum Cd concentrations may be associated with AD, but blood Cd concentrations not. Due to the limitation of quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： LIHui, MAOShao-ju, SUNWei-xuan, LIAOZhi-lin, TANGHan-mei, FUYan-yan, HUANGPeng. Correlation between Cadmium and Alzheimer's Disease:A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(9): 1030-1034. doi: 10.7507/1672-2531.20150172 Copy

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2.	Lindsay J, Anderson L. Dementia/Alzheimer's Disease. BMC Womens Health, 2004, 4(Suppl 1):S20.
3.	Hart RP, Rose CS, Hamer RM. Neuropsychological effects of occupational exposure to cadmium. J Clin Exp Neuropsychol, 1989, 11(6):933-943.
4.	Viaene MK, Masschelein R, Leenders J, et al. Neurobehavioural effects of occupational exposure to cadmium:a cross sectional epidemiological study. Occup Environ Med, 2000, 57(1):19-27.
5.	Emsley CL, Gao S, Li Y, Liang C, et al. Trace element levels in drinking water and cognitive function among elderly Chinese. Am J Epidemiol, 2000, 151(9):913-920.
6.	梁超轲, 吉荣娣, 曹静祥, 等. 饮水微量元素与老年人群认知能力关系研究. 卫生研究, 2004, 32(5):436-440.
7.	Gao S, Jin Y, Unverzagt FW, et al. Trace element levels and cognitive function in rural elderly Chinese. J Gerontol A Biol Sci Med Sci, 2008, 63(6):635-641.
8.	方宾, 赵广超. 老年痴呆患者血清中7种微量元素的测定与评价. 营养学报, 1997, 19(1):88-90.
9.	Bocca B, Forte G, Petrucci F, et al. Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease. Annali Dell'Istituto Superiore di Sanita, 2005, 41(2):197-203.
10.	刘勤勤, 赵雪慧, 黄河浪. 老年痴呆女性患者血液中九种化学元素分布特征与其患病关系的探讨. 中华疾病控制杂志, 2008, 12(6):587-590.
11.	闫冀, 黄河浪, 吴磊, 等. 城市社区老年痴呆患者全血中9种相关化学元素分布特征探讨. 现代预防医学, 2010, 37(14):2700-2705.
12.	刘坤彬. 血清微量元素水平与老年性痴呆和抑郁症的相关性研究. 山东:山东大学, 2008:7-8.
13.	李亚健, 张丽, 赵娜, 等. 血清金属元素含量与老年阿尔茨海默病的关系. 老年医学与保健, 2011, 17(5):304-306.
14.	Park JH, Lee DW, Park K, et al. Serum Trace Metal Levels in Alzheimer's Disease and Normal Control Groups. Am J Alzheimers Dis Other Demen, 2014, 29(1):76-83.
15.	González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Characterization of metal profiles in serum during the progression of Alzheimer's disease. Metallomic, 2014, 6(2):292-300.
16.	González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Homeostasis of metals in the progression of Alzheimer's disease. Biometals, 2014, 27(3):539-549.
17.	Basun H, Lind B, Nordberg M, et al. Cadmium in blood in Alzheimer's disease and non-demented subjects:results from a population-based study. Biometals, 1994, 7(2):130-134.
18.	Lee JY, Kim JH, Choi DW, et al. The Association of Heavy Metal of Blood and Serum in the Alzheimer's Diseases. Toxicol Res, 2012, 28(2):93-98.
19.	黄河浪, 吴磊, 吴一峰. 社区阿尔茨海默病患者血中相关化学元素神经递质的含量与分布特点. 中华疾病控制杂志, 2012, 16(5):382-387.
20.	唐骏. 基于宏量元素和神经递质检测的社区老年性痴呆人工神经网络预测模型研究. 南昌:南昌大学, 2012:26-27.
21.	González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Characterization of metal profiles in serum during the progression of Alzheimer's disease. Metallomic, 2014, 6(2):292-300.
22.	Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics. Science, 2002, 297(5580):353-356.
23.	李宵凌. EGCG对染镉APP/PS1小鼠Aβ影响的实验研究. 辽宁:中国医科大学, 2010:18-19.
24.	Peethumnongsin E, Yang L, Kallhoff-Muñoz V, et al. Convergence of presenilin-and tau-mediated pathways on axonal trafficking and neuronal function. J Neurosci, 2010, 30(40):13409-13418.
25.	Chen L, Liu L, Huang S. Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radic Biol Med, 2008, 45(7):1035-1044.
26.	袁燕, 江辰阳, 孙娅, 等. Cd对体外培养大鼠大脑皮质神经元钙稳态的影响. 中国兽医学报, 2013, 33(003):450-453.
27.	Goyer RA. Toxic and essential metal interactions. Annu Rev Nutr, 1997, 17(1):37-50.
28.	Visa M, Duta A. Methyl-orange and cadmium simultaneous removal using flyash and photo-Fenton systems. J Hazard Mater, 2013, (244-245):773-779.
29.	Sary AA, Beheshti M. Cadmium, iron, lead and mercury bioaccumulation in Abu Mullet, Liza abu, different tissues from Karoun and Karkheh Rivers, Khozestan, Iran. Bull Environ Contam Toxicol, 2012, 88(2):158-161.
30.	Son YO, Wang X, Hitron JA, et al. Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells. Toxicol Appl Pharmacol, 2011, 255(3):287-296.
31.	Valko M, Morris H, and Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem, 2005, 12(10):1161-1208.
32.	Son YO, Wang L, Poyil P, et al. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol, 2012, 264(2):153-160.
33.	Yamano T, De Cicco LA, Rikans LE. Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats:role of Kupffer cells and inflammatory cyto-kines. Toxicol Appl Pharmacol, 2000, 162(1):68-75.
34.	陈龙, 周娟, 高伟, 等. 镉负荷大鼠一氧化氮和肿瘤坏死因子-α释放在介导多器官机能活动障碍中的作用. 生理学报, 2003, 55(5):535-540.
35.	Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radic Biol Med, 2009, 46(9):1241-1249.

1. Selkoe DJ. Preventing Alzheimer's disease. Science, 2012, 337(6101):1488-1492.
2. Lindsay J, Anderson L. Dementia/Alzheimer's Disease. BMC Womens Health, 2004, 4(Suppl 1):S20.
3. Hart RP, Rose CS, Hamer RM. Neuropsychological effects of occupational exposure to cadmium. J Clin Exp Neuropsychol, 1989, 11(6):933-943.
4. Viaene MK, Masschelein R, Leenders J, et al. Neurobehavioural effects of occupational exposure to cadmium:a cross sectional epidemiological study. Occup Environ Med, 2000, 57(1):19-27.
5. Emsley CL, Gao S, Li Y, Liang C, et al. Trace element levels in drinking water and cognitive function among elderly Chinese. Am J Epidemiol, 2000, 151(9):913-920.
6. 梁超轲, 吉荣娣, 曹静祥, 等. 饮水微量元素与老年人群认知能力关系研究. 卫生研究, 2004, 32(5):436-440.
7. Gao S, Jin Y, Unverzagt FW, et al. Trace element levels and cognitive function in rural elderly Chinese. J Gerontol A Biol Sci Med Sci, 2008, 63(6):635-641.
8. 方宾, 赵广超. 老年痴呆患者血清中7种微量元素的测定与评价. 营养学报, 1997, 19(1):88-90.
9. Bocca B, Forte G, Petrucci F, et al. Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease. Annali Dell'Istituto Superiore di Sanita, 2005, 41(2):197-203.
10. 刘勤勤, 赵雪慧, 黄河浪. 老年痴呆女性患者血液中九种化学元素分布特征与其患病关系的探讨. 中华疾病控制杂志, 2008, 12(6):587-590.
11. 闫冀, 黄河浪, 吴磊, 等. 城市社区老年痴呆患者全血中9种相关化学元素分布特征探讨. 现代预防医学, 2010, 37(14):2700-2705.
12. 刘坤彬. 血清微量元素水平与老年性痴呆和抑郁症的相关性研究. 山东:山东大学, 2008:7-8.
13. 李亚健, 张丽, 赵娜, 等. 血清金属元素含量与老年阿尔茨海默病的关系. 老年医学与保健, 2011, 17(5):304-306.
14. Park JH, Lee DW, Park K, et al. Serum Trace Metal Levels in Alzheimer's Disease and Normal Control Groups. Am J Alzheimers Dis Other Demen, 2014, 29(1):76-83.
15. González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Characterization of metal profiles in serum during the progression of Alzheimer's disease. Metallomic, 2014, 6(2):292-300.
16. González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Homeostasis of metals in the progression of Alzheimer's disease. Biometals, 2014, 27(3):539-549.
17. Basun H, Lind B, Nordberg M, et al. Cadmium in blood in Alzheimer's disease and non-demented subjects:results from a population-based study. Biometals, 1994, 7(2):130-134.
18. Lee JY, Kim JH, Choi DW, et al. The Association of Heavy Metal of Blood and Serum in the Alzheimer's Diseases. Toxicol Res, 2012, 28(2):93-98.
19. 黄河浪, 吴磊, 吴一峰. 社区阿尔茨海默病患者血中相关化学元素神经递质的含量与分布特点. 中华疾病控制杂志, 2012, 16(5):382-387.
20. 唐骏. 基于宏量元素和神经递质检测的社区老年性痴呆人工神经网络预测模型研究. 南昌:南昌大学, 2012:26-27.
21. González-Domínguez R, García-Barrera T, Gómez-Ariza JL. Characterization of metal profiles in serum during the progression of Alzheimer's disease. Metallomic, 2014, 6(2):292-300.
22. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics. Science, 2002, 297(5580):353-356.
23. 李宵凌. EGCG对染镉APP/PS1小鼠Aβ影响的实验研究. 辽宁:中国医科大学, 2010:18-19.
24. Peethumnongsin E, Yang L, Kallhoff-Muñoz V, et al. Convergence of presenilin-and tau-mediated pathways on axonal trafficking and neuronal function. J Neurosci, 2010, 30(40):13409-13418.
25. Chen L, Liu L, Huang S. Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radic Biol Med, 2008, 45(7):1035-1044.
26. 袁燕, 江辰阳, 孙娅, 等. Cd对体外培养大鼠大脑皮质神经元钙稳态的影响. 中国兽医学报, 2013, 33(003):450-453.
27. Goyer RA. Toxic and essential metal interactions. Annu Rev Nutr, 1997, 17(1):37-50.
28. Visa M, Duta A. Methyl-orange and cadmium simultaneous removal using flyash and photo-Fenton systems. J Hazard Mater, 2013, (244-245):773-779.
29. Sary AA, Beheshti M. Cadmium, iron, lead and mercury bioaccumulation in Abu Mullet, Liza abu, different tissues from Karoun and Karkheh Rivers, Khozestan, Iran. Bull Environ Contam Toxicol, 2012, 88(2):158-161.
30. Son YO, Wang X, Hitron JA, et al. Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells. Toxicol Appl Pharmacol, 2011, 255(3):287-296.
31. Valko M, Morris H, and Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem, 2005, 12(10):1161-1208.
32. Son YO, Wang L, Poyil P, et al. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol, 2012, 264(2):153-160.
33. Yamano T, De Cicco LA, Rikans LE. Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats:role of Kupffer cells and inflammatory cyto-kines. Toxicol Appl Pharmacol, 2000, 162(1):68-75.
34. 陈龙, 周娟, 高伟, 等. 镉负荷大鼠一氧化氮和肿瘤坏死因子-α释放在介导多器官机能活动障碍中的作用. 生理学报, 2003, 55(5):535-540.
35. Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radic Biol Med, 2009, 46(9):1241-1249.

Chinese Journal of Evidence-Based Medicine

Correlation between Cadmium and Alzheimer's Disease:A Meta-analysis

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