{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:44:15Z","timestamp":1792017855434,"version":"4.4.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,9]]},"DOI":"10.7759\/cureus.46732","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T14:00:49Z","timestamp":1696860049000},"source":"Crossref","is-referenced-by-count":12,"title":["Exploring Methylene Blue and Its Derivatives in Alzheimer's Treatment: A Comprehensive Review of Randomized Control Trials"],"prefix":"10.7759","author":[{"given":"Muhammad Usman","family":"Hashmi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragda","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulafa","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kholood","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura M","family":"Bushra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areeg","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batran","family":"Elwadie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Madni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amel B","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadir","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132814","article-title":"A century of Alzheimer's disease","volume":"314","author":"Goedert M","year":"2006","unstructured":"Goedert M, Spillantini MG. A century of Alzheimer's disease. Science. 2006, 314:777-81. 10.1126\/science.1132814","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.43.8.1467","article-title":"Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease","volume":"43","author":"Saunders AM","year":"1993","unstructured":"Saunders AM, Strittmatter WJ, Schmechel D, et al.. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 1993, 43:1467-72. 10.1212\/wnl.43.8.1467","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1159\/000330020","article-title":"Vascular risk factors and dementia: 40-year follow-up of a population-based cohort","volume":"31","author":"R\u00f6nnemaa E","year":"2011","unstructured":"R\u00f6nnemaa E, Zethelius B, Lannfelt L, Kilander L. Vascular risk factors and dementia: 40-year follow-up of a population-based cohort. Dement Geriatr Cogn Disord. 2011, 31:460-6. 10.1159\/000330020","journal-title":"Dement Geriatr Cogn Disord"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1023\/a:1009068804787","article-title":"Traumatic brain injury as a risk factor for Alzheimer's disease: a review","volume":"10","author":"Lye TC","year":"2000","unstructured":"Lye TC, Shores EA. Traumatic brain injury as a risk factor for Alzheimer's disease: a review. Neuropsychol Rev. 2000, 10:115-29. 10.1023\/a:1009068804787","journal-title":"Neuropsychol Rev"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.6.2288","article-title":"Straight and paired helical filaments in Alzheimer disease have a common structural unit","volume":"88","author":"Crowther RA","year":"1991","unstructured":"Crowther RA. Straight and paired helical filaments in Alzheimer disease have a common structural unit. Proc Natl Acad Sci U S A. 1991, 88:2288-92. 10.1073\/pnas.88.6.2288","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1177\/10499091221116140","article-title":"End-of-life experiences within a dementia support program during COVID-19: context and circumstances surrounding death during the pandemic","volume":"40","author":"Brungardt A","year":"2023","unstructured":"Brungardt A, Cassidy J, LaRoche A, Dulaney S, Sawyer RJ, Possin KL, Lum HD. End-of-life experiences within a dementia support program during COVID-19: context and circumstances surrounding death during the pandemic. Am J Hosp Palliat Care. 2023, 40:778-83. 10.1177\/10499091221116140","journal-title":"Am J Hosp Palliat Care"},{"key":"ref7","unstructured":"2021 Alzheimer's disease facts and figures. (2021). Accessed. May 11, 2023: https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12328."},{"key":"ref8","unstructured":"2022 Alzheimer's disease facts and figures. (2022). Accessed. May 11, 2023: https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12638."},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70044-9","article-title":"Amyloid \u03b2 deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study","volume":"12","author":"Villemagne VL","year":"2013","unstructured":"Villemagne VL, Burnham S, Bourgeat P, et al.. Amyloid \u03b2 deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013, 12:357-67. 10.1016\/S1474-4422(13)70044-9","journal-title":"Lancet Neurol"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp062","article-title":"Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease","volume":"132","author":"Jack CR Jr","year":"2009","unstructured":"Jack CR Jr, Lowe VJ, Weigand SD, et al.. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain. 2009, 132:1355-65. 10.1093\/brain\/awp062","journal-title":"Brain"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak H","year":"1991","unstructured":"Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82:239-59. 10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-0081-6","article-title":"Methylene blue and its analogues as antidepressant compounds","volume":"32","author":"Delport A","year":"2017","unstructured":"Delport A, Harvey BH, Petzer A, Petzer JP. Methylene blue and its analogues as antidepressant compounds. Metab Brain Dis. 2017, 32:1357-82. 10.1007\/s11011-017-0081-6","journal-title":"Metab Brain Dis"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01462.x","article-title":"Methylene blue inhibits function of the 5-HT transporter","volume":"166","author":"Oz M","year":"2012","unstructured":"Oz M, Isaev D, Lorke DE, Hasan M, Petroianu G, Shippenberg TS. Methylene blue inhibits function of the 5-HT transporter. Br J Pharmacol. 2012, 166:168-76. 10.1111\/j.1476-5381.2011.01462.x","journal-title":"Br J Pharmacol"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-018-1045-3","article-title":"Efficacy and safety of methylene blue in the treatment of malaria: a systematic review","volume":"16","author":"Lu G","year":"2018","unstructured":"Lu G, Nagbanshi M, Goldau N, et al.. Efficacy and safety of methylene blue in the treatment of malaria: a systematic review. BMC Med. 2018, 16:59. 10.1186\/s12916-018-1045-3","journal-title":"BMC Med"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s002280000124","article-title":"Pharmacokinetics and organ distribution of intravenous and oral methylene blue","volume":"56","author":"Peter C","year":"2000","unstructured":"Peter C, Hongwan D, K\u00fcpfer A, Lauterburg BH. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000, 56:247-50. 10.1007\/s002280000124","journal-title":"Eur J Clin Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.10.033","article-title":"Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia\/reperfusion","volume":"1678","author":"Huang L","year":"2018","unstructured":"Huang L, Lu J, Cerqueira B, Liu Y, Jiang Z, Duong TQ. Chronic oral methylene blue treatment in a rat model of focal cerebral ischemia\/reperfusion. Brain Res. 2018, 1678:322-9. 10.1016\/j.brainres.2017.10.033","journal-title":"Brain Res"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-45","article-title":"Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden","volume":"5","author":"O'Leary JC 3rd","year":"2010","unstructured":"O'Leary JC 3rd, Li Q, Marinec P, et al.. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener. 2010, 5:45. 10.1186\/1750-1326-5-45","journal-title":"Mol Neurodegener"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079833","article-title":"Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study","volume":"8","author":"Shen Q","year":"2013","unstructured":"Shen Q, Du F, Huang S, Rodriguez P, Watts LT, Duong TQ. Neuroprotective efficacy of methylene blue in ischemic stroke: an MRI study. PLoS One. 2013, 8:e79833. 10.1371\/journal.pone.0079833","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.12659%2FMSM.907758","article-title":"Methylene blue exerts anticonvulsant and neuroprotective effects on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation in Wistar rats","volume":"24","author":"Cui ZQ","year":"2018","unstructured":"Cui ZQ, Li WL, Luo Y, et al.. Methylene blue exerts anticonvulsant and neuroprotective effects on self-sustaining status epilepticus (SSSE) induced by prolonged basolateral amygdala stimulation in Wistar rats. Med Sci Monit. 2018, 24:161-9. 10.12659%2FMSM.907758","journal-title":"Med Sci Monit"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9027-z","article-title":"Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy","volume":"15","author":"Rojas JC","year":"2009","unstructured":"Rojas JC, John JM, Lee J, Gonzalez-Lima F. Methylene blue provides behavioral and metabolic neuroprotection against optic neuropathy. Neurotox Res. 2009, 15:260-73. 10.1007\/s12640-009-9027-z","journal-title":"Neurotox Res"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25204866","article-title":"Use of biodegradable, chitosan-based nanoparticles in the treatment of Alzheimer's disease","volume":"25","author":"Manek E","year":"2020","unstructured":"Manek E, Darvas F, Petroianu GA. Use of biodegradable, chitosan-based nanoparticles in the treatment of Alzheimer's disease. Molecules. 2020, 25:4866. 10.3390\/molecules25204866","journal-title":"Molecules"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190772","article-title":"Concentration-dependent activity of hydromethylthionine on cognitive decline and brain atrophy in mild to moderate Alzheimer's disease","volume":"72","author":"Schelter BO","year":"2019","unstructured":"Schelter BO, Shiells H, Baddeley TC, et al.. Concentration-dependent activity of hydromethylthionine on cognitive decline and brain atrophy in mild to moderate Alzheimer's disease. J Alzheimers Dis. 2019, 72:931-46. 10.3233\/JAD-190772","journal-title":"J Alzheimers Dis"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170560","article-title":"Potential of low dose leuco-methylthioninium bis(hydromethanesulphonate) (LMTM) monotherapy for treatment of mild Alzheimer's disease: cohort analysis as modified primary outcome in a phase III clinical trial","volume":"61","author":"Wilcock GK","year":"2018","unstructured":"Wilcock GK, Gauthier S, Frisoni GB, et al.. Potential of low dose leuco-methylthioninium bis(hydromethanesulphonate) (LMTM) monotherapy for treatment of mild Alzheimer's disease: cohort analysis as modified primary outcome in a phase III clinical trial. J Alzheimers Dis. 2018, 61:435-57. 10.3233\/JAD-170560","journal-title":"J Alzheimers Dis"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31275-2","article-title":"Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial","volume":"388","author":"Gauthier S","year":"2016","unstructured":"Gauthier S, Feldman HH, Schneider LS, et al.. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016, 388:2873-84. 10.1016\/S0140-6736(16)31275-2","journal-title":"Lancet"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.219352","article-title":"Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease","volume":"352","author":"Baddeley TC","year":"2015","unstructured":"Baddeley TC, McCaffrey J, Storey JM, et al.. Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease. J Pharmacol Exp Ther. 2015, 352:110-8. 10.1124\/jpet.114.219352","journal-title":"J Pharmacol Exp Ther"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142874","article-title":"Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease","volume":"44","author":"Wischik CM","year":"2015","unstructured":"Wischik CM, Staff RT, Wischik DJ, et al.. Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease. J Alzheimers Dis. 2015, 44:705-20. 10.3233\/JAD-142874","journal-title":"J Alzheimers Dis"},{"key":"ref27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jalz.2008.05.438","article-title":"O3-04-07: Tau aggregation inhibitor (TAI) therapy with rember\u2122 arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks","volume":"4","author":"Wischik CM","year":"2008","unstructured":"Wischik CM, Bentham P, Wischik DJ, Seng KM. O3-04-07: Tau aggregation inhibitor (TAI) therapy with rember\u2122 arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks. Alzheimers Dement. 2008, 4:167-167.","journal-title":"Alzheimers Dement"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0529-0","article-title":"Tau biology and tau-directed therapies for Alzheimer's disease","volume":"76","author":"Bakota L","year":"2016","unstructured":"Bakota L, Brandt R. Tau biology and tau-directed therapies for Alzheimer's disease. Drugs. 2016, 76:301-13. 10.1007\/s40265-015-0529-0","journal-title":"Drugs"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2014.13101407","article-title":"Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia","volume":"171","author":"Telch MJ","year":"2014","unstructured":"Telch MJ, Bruchey AK, Rosenfield D, Cobb AR, Smits J, Pahl S, Gonzalez-Lima F. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. Am J Psychiatry. 2014, 171:1091-8. 10.1176\/appi.ajp.2014.13101407","journal-title":"Am J Psychiatry"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00197-z","article-title":"Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation","volume":"9","author":"Yang L","year":"2020","unstructured":"Yang L, Youngblood H, Wu C, Zhang Q. Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation. Transl Neurodegener. 2020, 9:19. 10.1186\/s40035-020-00197-z","journal-title":"Transl Neurodegener"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1038\/srep34784","article-title":"Attenuation of synaptic toxicity and MARK4\/PAR1-mediated tau phosphorylation by methylene blue for Alzheimer's disease treatment","volume":"6","author":"Sun W","year":"2016","unstructured":"Sun W, Lee S, Huang X, et al.. Attenuation of synaptic toxicity and MARK4\/PAR1-mediated tau phosphorylation by methylene blue for Alzheimer's disease treatment. Sci Rep. 2016, 6:34784. 10.1038\/srep34784","journal-title":"Sci Rep"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.2174\/1567201810666131113102037","article-title":"Preparation and characterization of methylene blue nanoparticles for Alzheimer's disease and other tauopathies","volume":"11","author":"Jinwal UK","year":"2014","unstructured":"Jinwal UK, Groshev A, Zhang J, Grover A, Sutariya VB. Preparation and characterization of methylene blue nanoparticles for Alzheimer's disease and other tauopathies. Curr Drug Deliv. 2014, 11:541-50. 10.2174\/1567201810666131113102037","journal-title":"Curr Drug Deliv"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00056","article-title":"Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation","volume":"7","author":"Xie L","year":"2013","unstructured":"Xie L, Li W, Winters A, Yuan F, Jin K, Yang S. Methylene blue induces macroautophagy through 5' adenosine monophosphate-activated protein kinase pathway to protect neurons from serum deprivation. Front Cell Neurosci. 2013, 7:56. 10.3389\/fncel.2013.00056","journal-title":"Front Cell Neurosci"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07581-2","article-title":"Shedding light on Alzheimer's \u03b2-amyloidosis: photosensitized methylene blue inhibits self-assembly of \u03b2-amyloid peptides and disintegrates their aggregates","volume":"7","author":"Lee BI","year":"2017","unstructured":"Lee BI, Suh YS, Chung YJ, Yu K, Park CB. Shedding light on Alzheimer's \u03b2-amyloidosis: photosensitized methylene blue inhibits self-assembly of \u03b2-amyloid peptides and disintegrates their aggregates. Sci Rep. 2017, 7:7523. 10.1038\/s41598-017-07581-2","journal-title":"Sci Rep"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.06.033","article-title":"Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model","volume":"76 Pt A","author":"Paban V","year":"2014","unstructured":"Paban V, Manrique C, Filali M, Maunoir-Regimbal S, Fauvelle F, Alescio-Lautier B. Therapeutic and preventive effects of methylene blue on Alzheimer's disease pathology in a transgenic mouse model. Neuropharmacology. 2014, 76 Pt A:68-79. 10.1016\/j.neuropharm.2013.06.033","journal-title":"Neuropharmacology"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-011613-135932","article-title":"Emerging therapeutics for Alzheimer's disease","volume":"54","author":"Chiang K","year":"2014","unstructured":"Chiang K, Koo EH. Emerging therapeutics for Alzheimer's disease. Annu Rev Pharmacol Toxicol. 2014, 54:381-405. 10.1146\/annurev-pharmtox-011613-135932","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2020.1719066","article-title":"An evaluation of hydromethylthionine as a treatment option for Alzheimer's disease","volume":"21","author":"Hashweh NN","year":"2020","unstructured":"Hashweh NN, Bartochowski Z, Khoury R, Grossberg GT. An evaluation of hydromethylthionine as a treatment option for Alzheimer's disease. Expert Opin Pharmacother. 2020, 21:619-27. 10.1080\/14656566.2020.1719066","journal-title":"Expert Opin Pharmacother"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/154706-exploring-methylene-blue-and-its-derivatives-in-alzheimers-treatment-a-comprehensive-review-of-randomized-control-trials","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T19:53:31Z","timestamp":1707508411000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/154706-exploring-methylene-blue-and-its-derivatives-in-alzheimers-treatment-a-comprehensive-review-of-randomized-control-trials"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,9]]},"references-count":37,"URL":"https:\/\/doi.org\/10.7759\/cureus.46732","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,9]]}}}