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Review | Open Access

Magnesium ions and dementia

Pei XuaDehua Cuib( )Mingyue Jina( )Liyuan Suna( )
Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University, Guilin 541199, Guangxi, China
Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology and Department of Neurology, Peking University Third Hospital, Beijing 100191, China
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Abstract

Magnesium is an essential nutrient involved in a wide range of physiological activities to maintain normal brain functions. So far, magnesium has been recognized as a cofactor for over 600 enzymatic reactions within the body. Importantly, magnesium deficiency has been implicated in the pathogenesis of various dementia-related diseases containing cardiovascular diseases and Alzheimer’s disease (AD). With increased aging, the incidence and prevalence of dementia are expected to rise dramatically double every 20 years worldwide. Accumulating evidence indicates that dementia-related diseases are associated with low magnesium levels, and dietary magnesium intake can improve cognitive function. Many studies have revealed that magnesium ions act as a natural Ca2+ blocker to inhibit calcium overload and halt the course of AD by blocking N-methyl-D-aspartate receptors and thus inhibiting neuronal overactivation. In addition, magnesium ions can inhibit glial cell-mediated neuroinflammation by down-regulating pro-inflammatory cytokines and oxidative stress, which have been implicated in the development of chronic age-related diseases. Thus, magnesium may be a target for the prevention and treatment of neurological diseases. Taken together, maintaining an optimal magnesium balance may help in the prevention of cognitive decline and dementia. In this review, we summarize our current understanding of the role of magnesium in dementia, highlighting recent progresses in the field.

References

1

Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112–2117. https://doi.org/10.1016/s0140-6736(05)67889-0.

2

Li G, Shen YC, Chen CH, et al. An epidemiological survey of age-related dementia in an urban area of Beijing. Acta Psychiatr Scand. 1989;79(6):557–563. https://doi.org/10.1111/j.1600-0447.1989.tb10303.x.

3

Helzner EP, Luchsinger JA, Scarmeas N, et al. Contribution of vascular risk factors to the progression in Alzheimer disease. Arch Neurol. 2009;66(3):343–348. https://doi.org/10.1001/archneur.66.3.343.

4

Skoog I. Status of risk factors for vascular dementia. Neuroepidemiology. 1998;17(1):2–9. https://doi.org/10.1159/000026147.

5

Davey DA. Alzheimer's disease and vascular dementia: one potentially preventable and modifiable disease. Part I: pathology, diagnosis and screening. Neurodegener Dis Manag. 2014;4(3):253–259. https://doi.org/10.2217/nmt.14.14.

6

Reddy ST, Soman SS, Yee J. Magnesium balance and measurement. Adv Chron Kidney Dis. 2018;25(3):224–229. https://doi.org/10.1053/j.ackd.2018. 03.002.

7

Ventskivs’ka IB, Senchuk AI. Role of magnesium in the pathogenesis of premenstrual disorders. Lik Sprava. 2005;(8):62–65.

8

Barbagallo M, Veronese N, Dominguez LJ. Magnesium in aging, health and diseases. Nutrients. 2021;13(2):463. https://doi.org/10.3390/nu13020463.

9

Muir KW. Magnesium in stroke treatment. Postgrad Med. 2002;78(925):641–645. https://doi.org/10.1136/pmj.78.925.641.

10

Rinösl H, Skhirtladze K, Felli A, et al. The neuroprotective effect of magnesium sulphate during iatrogenically-induced ventricular fibrillation. Magnes Res. 2013;26(3):109–119. https://doi.org/10.1684/mrh.2013.0345.

11

Afshari D, Moradian N, Rezaei M. Evaluation of the intravenous magnesium sulfate effect in clinical improvement of patients with acute ischemic stroke. Clin Neurol Neurosurg. 2013;115(4):400–404. https://doi.org/10.1016/j.clineuro.2012.06.001.

12

Lou Z, Ren KD, Tan B, et al. Salviaolate protects rat brain from ischemia-reperfusion injury through inhibition of NADPH oxidase. Planta Med. 2015;81(15):1361–1369. https://doi.org/10.1055/s-0035-1557774.

13

Clerc P, Young CA, Bordt EA, et al. Magnesium sulfate protects against the bioenergetic consequences of chronic glutamate receptor stimulation. PLoS One. 2013;8(11):e79982. https://doi.org/10.1371/journal.pone.0079982.

14

Wang P, Yu X, Guan PP, et al. Magnesium ion influx reduces neuroinflammation in Aβ precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin-1β. Cell Mol Immunol. 2017;14(5):451–464. https://doi.org/10.1038/cmi.2015.93.

15

Veronese N, Zurlo A, Solmi M, et al. Magnesium status in Alzheimer's disease: a systematic review. Am J Alzheimers Dis Other Demen. 2016;31(3):208–213. https://doi.org/10.1177/1533317515602674.

16

Wilmott LA, Thompson LT. Sex- and dose-dependent effects of post-trial calcium channel blockade by magnesium chloride on memory for inhibitory avoidance conditioning. Behav Brain Res. 2013;257:49–53. https://doi.org/10.1016/j.bbr.2013.09.047.

17

Lamhot VB, Khatib N, Ginsberg Y, et al. Magnesium sulfate prevents maternal inflammation-induced impairment of learning ability and memory in rat offspring. Am J Obstet Gynecol. 2015;213(6):851. https://doi.org/10.1016/j.ajog.2015.07.042.e1-8.

18

Slutsky I, Abumaria N, Wu LJ, et al. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010;65(2):165–177. https://doi.org/10.1016/j.neuron.2009.12.026.

19

Abumaria N, Yin B, Zhang L, et al. Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. J Neurosci. 2011;31(42):14871–14881. https://doi.org/10.1523/jneurosci.3782-11.2011.

20

Bardgett ME, Schultheis PJ, McGill DL, et al. Magnesium deficiency impairs fear conditioning in mice. Brain Res. 2005;1038(1):100–106. https://doi.org/10.1016/j.brainres.2005.01.020.

21

Danysz W, Parsons CG. The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatr. 2003;18(suppl 1):S23–S32. https://doi.org/10.1002/gps.938.

22

Ozturk S, Cillier AE. Magnesium supplementation in the treatment of dementia patients. Med Hypotheses. 2006;67(5):1223–1225. https://doi.org/10.1016/j.mehy.2006.04.047.

23

Kirkland AE, Sarlo GL, Holton KF. The role of magnesium in neurological disorders. Nutrients. 2018;10(6):730. https://doi.org/10.3390/nu100 60730.

24

Yasui M, Ota K. Serum concentrations of magnesium and parathyroid hormone in randomly selected hospital in-patients and out-patients, and in in-patients with dementia. J Int Med Res. 1992;20(4):313–322. https://doi.org/10.1177/030006059202000402.

25

Bayer KU, De Koninck P, Leonard AS, et al. Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature. 2001;411(6839):801–805. https://doi.org/10.1038/35081080.

26

Bayer KU, LeBel E, McDonald GL, et al. Transition from reversible to persistent binding of CaMKII to postsynaptic sites and NR2B. J Neurosci. 2006;26(4):1164–1174. https://doi.org/10.1523/jneurosci.3116-05.2006.

27

Bi H, Sze CI. N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease. J Neurol Sci. 2002;200(1/2):11–18. https://doi.org/10.1016/s0022-510x(02)00087-4.

28

Gaffney-Stomberg E. The impact of trace minerals on bone metabolism. Biol Trace Elem Res. 2019;188(1):26–34. https://doi.org/10.1007/s12011-018-1583-8.

29

Andrási E, Igaz S, Molnár Z, et al. Disturbances of magnesium concentrations in various brain areas in Alzheimer's disease. Magnes Res. 2000;13(3):189–196.

30

Borella P, Giardino A, Neri M, et al. Magnesium and potassium status in elderly subjects with and without dementia of the Alzheimer type. Magnes Res. 1990;3(4):283–289.

31

Cilliler AE, Ozturk S, Ozbakir S. Serum magnesium level and clinical deterioration in Alzheimer's disease. Gerontology. 2007;53(6):419–422. https://doi.org/10.1159/000110873.

32

Gerhardsson L, Blennow K, Lundh T, et al. Concentrations of metals, beta-amyloid and tau-markers in cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2009;28(1):88–94. https://doi.org/10.1159/000233353.

33

Gerhardsson L, Lundh T, Minthon L, et al. Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2008;25(6):508–515. https://doi.org/10.1159/000129365.

34

Basun H, Forssell LG, Wetterberg L, et al. Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer's disease. J Neural Transm Park Dis Dement Sect. 1991;3(4):231–258.

35

Babić Leko M, Mihelčić M, Jurasović J, et al. Heavy metals and essential metals are associated with cerebrospinal fluid biomarkers of Alzheimer's disease. Int J Mol Sci. 2022;24(1):467. https://doi.org/10.3390/ijms24010467.

36

Deane R, Yan SD, Submamaryan RK, et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med. 2003;9(7):907–913. https://doi.org/10.1038/nm890.

37

Deane R, Wu ZH, Sagare A, et al. LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron. 2004;43(3):333–344. https://doi.org/10.1016/j.neuron.2004.07.017.

38

Shibata M, Yamada S, Kumar SR, et al. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest. 2000;106(12):1489–1499. https://doi.org/10.1172/jci10498.

39

Kanekiyo T, Liu CC, Shinohara M, et al. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-B. J Neurosci. 2012;32(46):16458–16465. https://doi.org/10.1523/jneurosci.3987-12.2012.

40

Zhu DH, Su YC, Fu BM, et al. Magnesium reduces blood-brain barrier permeability and regulates amyloid-β transcytosis. Mol Neurobiol. 2018;55(9):7118–7131. https://doi.org/10.1007/s12035-018-0896-0.

41

Yu J, Sun M, Chen Z, et al. Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimers Dis. 2010;20(4):1091–1106. https://doi.org/10.3233/jad-2010-091444.

42

De Reuck J, Decoo D, Marchau M, et al. Positron emission tomography in vascular dementia. J Neurol Sci. 1998;154(1):55–61. https://doi.org/10.1016/s0022-510x(97)00213-x.

43

Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–866. https://doi.org/10.1016/j.neuron.2013.10.008.

44

Shabir O, Berwick J, Francis SE. Neurovascular dysfunction in vascular dementia, Alzheimer's and atherosclerosis. BMC Neurosci. 2018;19(1):62. https://doi.org/10.1186/s12868-018-0465-5.

45

van den Bergh WM, Zuur JK, Kamerling NA, et al. Role of magnesium in the reduction of ischemic depolarization and lesion volume after experimental subarachnoid hemorrhage. J Neurosurg. 2002;97(2):416–422. https://doi.org/10.3171/jns.2002.97.2.0416.

46

Nowak L, Bregestovski P, Ascher P, et al. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984;307(5950):462–465. https://doi.org/10.1038/307462a0.

47

Parsons CG, Danysz W, Quack G. Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect. 1998;11(9):523–569. https://doi.org/10.1358/dnp.1998.11.9.863689.

48

Doraiswamy PM. Alzheimer's disease and the glutamate NMDA receptor. Psychopharmacol Bull. 2003;37(2):41–49.

49

Jain KK. Evaluation of memantine for neuroprotection in dementia. Expet Opin Invest Drugs. 2000;9(6):1397–1406. https://doi.org/10.1517/13543784.9.6.1397.

50

Gao J, Duan B, Wang DG, et al. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron. 2005;48(4):635–646. https://doi.org/10.1016/j.neuron.2005.10.011.

51

Barria A, Malinow R. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron. 2005;48(2):289–301. https://doi.org/10.1016/j.neuron.2005.08.034.

52

Kass IS, Cottrell JE, Chambers G. Magnesium and cobalt, not nimodipine, protect neurons against anoxic damage in the rat hippocampal slice. Anesthesiology. 1988;69(5):710–715. https://doi.org/10.1097/00000542-198811000-00012.

53

Vener AV, Aksenova MV, Burbaeva GS. Drastic reduction of the zinc- and magnesium-stimulated protein tyrosine kinase activities in Alzheimer's disease hippocampus. FEBS Lett. 1993;328(1/2):6–8. https://doi.org/10.1016/0014-5793(93)80953-r.

54

Malchiodi-Albedi F, Paradisi S, Matteucci A, et al. Amyloid oligomer neurotoxicity, calcium dysregulation, and lipid rafts. Int J Alzheimer's Dis. 2011;2011: 906964. https://doi.org/10.4061/2011/906964.

55

Schilling T, Eder C. Amyloid-β-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia. J Cell Physiol. 2011;226(12):3295–3302. https://doi.org/10.1002/jcp.22675.

56

Mattson MP, Chan SL. Neuronal and glial calcium signaling in Alzheimer's disease. Cell Calcium. 2003;34(4/5):385–397. https://doi.org/10.1016/s0143-4160(03)00128-3.

57

Gao F, Ding BZ, Zhou LA, et al. Magnesium sulfate provides neuroprotection in lipopolysaccharide-activated primary microglia by inhibiting NF-κB pathway. J Surg Res. 2013;184(2):944–950. https://doi.org/10.1016/j.jss.2013.03.034.

58

Nagele RG, D'Andrea MR, Lee H, et al. Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res. 2003;971(2):197–209. https://doi.org/10.1016/s0006-8993(03)02361-8.

59

Town T, Nikolic V, Tan J. The microglial “activation” continuum: from innate to adaptive responses. J Neuroinflammation. 2005;2:24. https://doi.org/10.1186/1742-2094-2-24.

60

Yamamoto M, Kiyota T, Horiba M, et al. Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice. Am J Pathol. 2007;170(2):680–692. https://doi.org/10.2353/ajpath.2007.060378.

61

Liao YF, Wang BJ, Cheng HT, et al. Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004;279(47):49523–49532. https://doi.org/10.1074/jbc.M402034200.

62

Hickman SE, Allison EK, El Khoury J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer's disease mice. J Neurosci. 2008;28(33):8354–8360. https://doi.org/10.1523/jneurosci.0616-08.2008.

63

Kitazawa M, Cheng D, Tsukamoto MR, et al. Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal β-catenin pathway function in an Alzheimer's disease model. J Immunol. 2011;187(12):6539–6549. https://doi.org/10.4049/jimmunol.1100620.

64

Rochelson B, Dowling O, Schwartz N, et al. Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway. J Reprod Immunol. 2007;73(2):101–107. https://doi.org/10.1016/j.jri.2006.06.004.

65

Li XL, Liu HS, Yang YY. Magnesium sulfate attenuates brain edema by lowering AQP4 expression and inhibits glia-mediated neuroinflammation in a rodent model of eclampsia. Behav Brain Res. 2019;364:403–412. https://doi.org/10.1016/j.bbr.2017.12.031.

66

Andrási E, Páli N, Molnár Z, et al. Brain aluminum, magnesium and phosphorus contents of control and Alzheimer-diseased patients. J Alzheimers Dis. 2005;7(4):273–284. https://doi.org/10.3233/jad-2005-7402.

67

Atabek ME, Kurtoglu S, Pirgon O, et al. Serum magnesium concentrations in type 1 diabetic patients: relation to early atherosclerosis. Diabetes Res Clin Pract. 2006;72(1):42–47. https://doi.org/10.1016/j.diabres.2005.09.002.

68

Sinclair AJ, Bayer AJ, Johnston J, et al. Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia. Int J Geriatr Psychiatr. 1998;13(12):840–845. https://doi.org/10.1002/(sici)1099-1166(1998120)13:12<840::aid-gps877>3.0.co;2-r.

69

Garcia LA, Dejong SC, Martin SM, et al. Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion model. J Am Coll Cardiol. 1998;32(2):536–539. https://doi.org/10.1016/s0735-1097(98)00231-9.

70

Regan RF, Jasper E, Guo Y, et al. The effect of magnesium on oxidative neuronal injury in vitro. J Neurochem. 1998;70(1):77–85. https://doi.org/10.1046/j.1471-4159.1998.70010077.x.

71

Back SA, Kroenke CD, Sherman LS, et al. White matter lesions defined by diffusion tensor imaging in older adults. Ann Neurol. 2011;70(3):465–476. https://doi.org/10.1002/ana.22484.

72

Kaiser D, Weise GS, Möller K, et al. Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease. Acta Neuropathol Commun. 2014;2:169. https://doi.org/10.1186/s40478-014-0169-8.

73

Metti AL, Yaffe K, Boudreau RM, et al. Trajectories of inflammatory markers and cognitive decline over 10 years. Neurobiol Aging. 2014;35(12):2785–2790. https://doi.org/10.1016/j.neurobiolaging.2014.05.030.

74

Crehan H, Hardy J, Pocock J. Blockage of CR1 prevents activation of rodent microglia. Neurobiol Dis. 2013;54:139–149. https://doi.org/10.1016/j.nbd.2013.02.003.

75

Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol. 2012;34(1):43–62. https://doi.org/10.1007/s00281-011-0290-8.

76

Cohen RA, Tong XY. Vascular oxidative stress: the common link in hypertensive and diabetic vascular disease. J Cardiovasc Pharmacol. 2010;55(4):308–316. https://doi.org/10.1097/fjc.0b013e3181d89670.

77

Xu RS. Pathogenesis of diabetic cerebral vascular disease complication. World J Diabetes. 2015;6(1):54–66. https://doi.org/10.4239/wjd.v6.i1.54.

78

Belin RJ, He K. Magnesium physiology and pathogenic mechanisms that contribute to the development of the metabolic syndrome. Magnes Res. 2007;20(2):107–129.

79

Luo JJ, Lan HW, Jiang JJ, et al. Effect of magnesium L-threonate on chronic cerebral hypoperfusion-induced cerebral white matter injury in patients. Chin J Hematol. 2022;35(5):8–12. https://doi.org/10.19296/j.cnki.1008-2409.2022-05-002.

80

de Baaij JHF, Hoenderop JGJ, Bindels RJM. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46. https://doi.org/10.1152/physrev.00012.2014.

81

Okumoto Y, Koyama E, Matsubara H, et al. Sleep improvement by light in a demented aged individual. Psychiatr Clin Neurosci. 1998;52(2):194–196. https://doi.org/10.1111/j.1440-1819.1998.tb01026.x.

82

You HJ, Cho SE, Kang SG, et al. Decreased serum magnesium levels in depression: a systematic review and meta-analysis. Nord J Psychiatr. 2018;72(7):534–541. https://doi.org/10.1080/08039488.2018.1538388.

83

Botturi A, Ciappolino V, Delvecchio G, et al. The role and the effect of magnesium in mental disorders: a systematic review. Nutrients. 2020;12(6):1661. https://doi.org/10.3390/nu12061661.

84

Phelan D, Molero P, Martínez-González MA, et al. Magnesium and mood disorders: systematic review and meta-analysis. BJPsych Open. 2018;4(4):167–179. https://doi.org/10.1192/bjo.2018.22.

85

Sanders O, Rajagopal L. Phosphodiesterase inhibitors for Alzheimer's disease: a systematic review of clinical trials and epidemiology with a mechanistic rationale. J Alzheimers Dis Rep. 2020;4(1):185–215. https://doi.org/10.3233/ADR-200191.

86

Zhao X, Liu J, Yang S, et al. A novel pharmacodynamic model in rats for preventing vascular dementia from maintaining neurovascular coupling sensitivity. Eur J Pharmacol. 2018;827:149–158. https://doi.org/10.1016/j.ejphar.2018.03.010.

87

Okada M, Kaneko S. Pharmacological interactions between magnesium ion and adenosine on monoaminergic system in the central nervous system. Magnes Res. 1998;11(4):289–305.

88

Iotti S, Malucelli E. In vivo assessment of Mg2+ in human brain and skeletal muscle by 31P-MRS. Magnes Res. 2008;21(3):157–162.

Journal of Neurorestoratology
Article number: 100094
Cite this article:
Xu P, Cui D, Jin M, et al. Magnesium ions and dementia. Journal of Neurorestoratology, 2024, 12(1): 100094. https://doi.org/10.1016/j.jnrt.2024.100094

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Received: 12 July 2023
Revised: 28 November 2023
Accepted: 25 December 2023
Published: 12 January 2024
© 2024.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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