{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:38:40Z","timestamp":1764175120340,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL70825"],"award-info":[{"award-number":["R01-HL70825"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01, 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917"],"award-info":[{"award-number":["U01, 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 \u00b1 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011\u20132013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention.<\/jats:p>","DOI":"10.3390\/nu13124496","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T21:32:40Z","timestamp":1639690360000},"page":"4496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Aniqa B.","family":"Alam","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Emory University School of Public Health, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DaNashia S.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Psychology, School of Arts and Sciences, Clark Atlanta University, Atlanta, GA 30314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-1340","authenticated-orcid":false,"given":"Pamela L.","family":"Lutsey","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55454, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srishti","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Neurology and the MIND Center, University of Mississippi Medical Center, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2225-8323","authenticated-orcid":false,"given":"Alvaro","family":"Alonso","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Emory University School of Public Health, Atlanta, GA 30322, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alam, A.B., Lutsey, P.L., Gottesman, R.F., Tin, A., and Alonso, A. (2020). Low Serum Magnesium is Associated with Incident Dementia in the ARIC-NCS Cohort. Nutrients, 12.","DOI":"10.3390\/nu12103074"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1212\/WNL.0000000000004517","article-title":"Serum magnesium is associated with the risk of dementia","volume":"89","author":"Kieboom","year":"2017","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13041-014-0065-y","article-title":"Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer\u2019s disease mouse model","volume":"7","author":"Li","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/cns.12775","article-title":"Magnesium boosts the memory restorative effect of environmental enrichment in Alzheimer\u2019s disease mice","volume":"24","author":"Huang","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.0954-6820.1981.tb02648.x","article-title":"Magnesium deficiency. Etiology and clinical spectrum","volume":"647","author":"Flink","year":"1981","journal-title":"Acta Med. Scand Suppl."},{"key":"ref_6","first-page":"226","article-title":"Role of magnesium and potassium in the pathogenesis of arteriosclerosis","volume":"3","author":"Rayssiguier","year":"1984","journal-title":"Magnesium"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1067\/mhj.2000.107553","article-title":"Low intracellular magnesium levels promote platelet-dependent thrombosis in patients with coronary artery disease","volume":"140","author":"Shechter","year":"2000","journal-title":"Am. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1001\/jamaneurol.2017.1658","article-title":"Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort","volume":"74","author":"Gottesman","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_9","unstructured":"Gragossian, A., Bashir, K., and Friede, R. (2021). Hypomagnesemia, StatPearls."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2147\/IJNRD.S42054","article-title":"Hypomagnesemia: A clinical perspective","volume":"7","author":"Pham","year":"2014","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bbadis.2004.02.004","article-title":"High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro","volume":"1689","author":"Maier","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1089\/neu.2000.17.857","article-title":"Neuronal apoptosis after CNS injury: The roles of glutamate and calcium","volume":"17","author":"Zipfel","year":"2000","journal-title":"J. Neurotrauma"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e944","DOI":"10.1212\/WNL.0000000000007001","article-title":"Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study","volume":"92","author":"Larsson","year":"2019","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/08037051.2012.759696","article-title":"Relationship of serum magnesium concentration to risk of short-term outcome of acute ischemic stroke","volume":"22","author":"Feng","year":"2013","journal-title":"Blood Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1161\/01.STR.0000105928.95124.1F","article-title":"Low serum magnesium predicts neurological events in patients with advanced atherosclerosis","volume":"35","author":"Amighi","year":"2004","journal-title":"Stroke"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1016\/j.jacc.2021.04.035","article-title":"The ARIC (Atherosclerosis Risk in Communities) Study: JACC Focus Seminar 3\/8","volume":"77","author":"Wright","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_17","first-page":"1","article-title":"Mild Cognitive Impairment and Dementia Prevalence: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)","volume":"2","author":"Knopman","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1161\/STROKEAHA.114.007847","article-title":"Vascular imaging abnormalities and cognition: Mediation by cortical volume in nondemented individuals: Atherosclerosis risk in communities-neurocognitive study","volume":"46","author":"Knopman","year":"2015","journal-title":"Stroke"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0896-6273(02)00569-X","article-title":"Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain","volume":"33","author":"Fischl","year":"2002","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.numecd.2020.03.010","article-title":"Circulating electrolytes and the prevalence of atrial fibrillation and supraventricular ectopy: The Atherosclerosis Risk in Communities (ARIC) study","volume":"30","author":"Alonso","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.31887\/DCNS.2000.2.3\/jnewcomer","article-title":"NMDA receptor function, memory, and brain aging","volume":"2","author":"Newcomer","year":"2000","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"761","DOI":"10.2174\/1389203715666140903145608","article-title":"Relationship between Na+, K+-ATPase and NMDA receptor at central synapses","volume":"15","author":"Bersier","year":"2014","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"746","DOI":"10.2174\/156720512801322564","article-title":"N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer\u2019s disease, vascular dementia and Parkinson\u2019s disease","volume":"9","author":"Olivares","year":"2012","journal-title":"Curr. Alzheimer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.neuint.2004.03.007","article-title":"Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer\u2019s disease","volume":"45","author":"Hynd","year":"2004","journal-title":"Neurochem. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.jalz.2014.05.1755","article-title":"Reduced cerebrovascular reactivity in young adults carrying the APOE epsilon4 allele","volume":"11","author":"Suri","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000069132","article-title":"Ultrastructure of the optic nerve in magnesium-deficient rats","volume":"35","author":"Gong","year":"2003","journal-title":"Ophthalmic Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s11011-019-00419-y","article-title":"Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats","volume":"34","author":"Shadman","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.ajpath.2019.11.004","article-title":"Endothelial Cell Calcium Signaling during Barrier Function and Inflammation","volume":"190","author":"Dalal","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1161\/STROKEAHA.114.005917","article-title":"Plasma magnesium and risk of ischemic stroke among women","volume":"45","author":"Adebamowo","year":"2014","journal-title":"Stroke"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1161\/01.CIR.102.19.2353","article-title":"Oral magnesium therapy improves endothelial function in patients with coronary artery disease","volume":"102","author":"Shechter","year":"2000","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1093\/clinchem\/33.11.1965","article-title":"Assessment of magnesium status","volume":"33","author":"Elin","year":"1987","journal-title":"Clin. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0011-5029(88)90013-2","article-title":"Magnesium metabolism in health and disease","volume":"34","author":"Elin","year":"1988","journal-title":"Dis. Mon."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S1359-6446(00)01632-9","article-title":"Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1)","volume":"6","author":"Kusuhara","year":"2001","journal-title":"Drug Discov. Today."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.aca.2008.08.018","article-title":"Speciation analysis of selected metals and determination of their total contents in paired serum and cerebrospinal fluid samples: An approach to investigate the permeability of the human blood-cerebrospinal fluid-barrier","volume":"627","author":"Nischwitz","year":"2008","journal-title":"Anal. Chim. Acta."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-2236(03)00067-5","article-title":"The metallobiology of Alzheimer\u2019s disease","volume":"26","author":"Bush","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0021-9258(19)35418-3","article-title":"Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma","volume":"263","author":"Vink","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"685","DOI":"10.4103\/ajns.AJNS_232_16","article-title":"Serum Magnesium as a Marker of Neurological Outcome in Severe Traumatic Brain Injury Patients","volume":"13","author":"Nayak","year":"2018","journal-title":"Asian J. Neurosurg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/STROKEAHA.107.492934","article-title":"Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats","volume":"39","author":"Lecrux","year":"2008","journal-title":"Stroke"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1161\/01.STR.0000259628.94421.09","article-title":"Magnesium for treatment of acute lacunar stroke syndromes: Further analysis of the IMAGES trial","volume":"38","author":"Aslanyan","year":"2007","journal-title":"Stroke"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Lutsey, P.L., Chen, L.Y., Eaton, A., Jaeb, M., Rudser, K.D., Neaton, J.D., and Alonso, A. (2018). A Pilot Randomized Trial of Oral Magnesium Supplementation on Supraventricular Arrhythmias. Nutrients, 10.","DOI":"10.3390\/nu10070884"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:13Z","timestamp":1760168953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/12\/4496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["nu13124496"],"URL":"https:\/\/doi.org\/10.3390\/nu13124496","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2021,12,16]]}}}