{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:45:22Z","timestamp":1790279122623,"version":"4.1.0"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drugs Aging"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1007\/s40266-019-00649-w","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T10:54:29Z","timestamp":1554375269000},"page":"419-434","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis"],"prefix":"10.1007","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-7880","authenticated-orcid":false,"given":"Andrew H.","family":"Ford","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo P.","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"issue":"6","key":"649_CR1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nrneurol.2017.63","volume":"13","author":"YT Wu","year":"2017","unstructured":"Wu YT, Beiser AS, Breteler MMB, et al. The changing prevalence and incidence of dementia over time: current evidence. Nat Rev Neurol. 2017;13(6):327\u201339.","journal-title":"Nat Rev Neurol."},{"key":"649_CR2","doi-asserted-by":"publisher","first-page":"b158","DOI":"10.1136\/bmj.b158","volume":"338","author":"A Burns","year":"2009","unstructured":"Burns A, Iliffe S. Alzheimer\u2019s disease. BMJ. 2009;338:b158.","journal-title":"BMJ"},{"issue":"10113","key":"649_CR3","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1016\/S0140-6736(17)31363-6","volume":"390","author":"G Livingston","year":"2017","unstructured":"Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673\u20134.","journal-title":"Lancet"},{"issue":"6","key":"649_CR4","first-page":"367","volume":"14","author":"H Droller","year":"1959","unstructured":"Droller H, Dossett JA. Vitamin B12 levels in senile dementia and confusional states. Geriatrics. 1959;14(6):367\u201373.","journal-title":"Geriatrics."},{"issue":"6","key":"649_CR5","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1001\/archinte.1918.00090110088005","volume":"XXI","author":"HW Woltman","year":"1918","unstructured":"Woltman HW. Brain changes associated with pernicious anemia. Arch Intern Med. 1918;XXI(6):791\u2013843.","journal-title":"Arch Intern Med."},{"issue":"3","key":"649_CR6","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1176\/jnp.12.3.389","volume":"12","author":"N Goebels","year":"2000","unstructured":"Goebels N, Soyka M. Dementia associated with vitamin B(12) deficiency: presentation of two cases and review of the literature. J Neuropsychiatry Clin Neurosci. 2000;12(3):389\u201394.","journal-title":"J Neuropsychiatry Clin Neurosci"},{"issue":"5","key":"649_CR7","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/mp.2011.18","volume":"17","author":"AH Ford","year":"2012","unstructured":"Ford AH, Flicker L, Hankey GJ, et al. Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and cognitive impairment: the health in men study. Mol Psychiatry. 2012;17(5):559\u201366.","journal-title":"Mol Psychiatry."},{"issue":"2 Suppl.","key":"649_CR8","doi-asserted-by":"publisher","first-page":"S143","DOI":"10.1177\/15648265080292S119","volume":"29","author":"AD Smith","year":"2008","unstructured":"Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008;29(2 Suppl.):S143\u201372.","journal-title":"Food Nutr Bull."},{"issue":"3","key":"649_CR9","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.archger.2008.03.009","volume":"48","author":"F Dam Van","year":"2009","unstructured":"Van Dam F, Van Gool WA. Hyperhomocysteinemia and Alzheimer\u2019s disease: a systematic review. Arch Gerontol Geriatr. 2009;48(3):425\u201330.","journal-title":"Arch Gerontol Geriatr"},{"issue":"7135","key":"649_CR10","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1136\/bmj.316.7135.894","volume":"316","author":"Homocysteine Lowering Trialists\u2019 Collaboration","year":"1998","unstructured":"Homocysteine Lowering Trialists\u2019 Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists\u2019 Collaboration. BMJ. 1998;316(7135):894\u20138.","journal-title":"BMJ."},{"issue":"1","key":"649_CR11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3233\/JAD-2012-111739","volume":"29","author":"AH Ford","year":"2012","unstructured":"Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133\u201349.","journal-title":"J Alzheimers Dis."},{"issue":"3","key":"649_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein MF, Folstein SE, McHugh PR. \u201cMini-mental state\u201d: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189\u201398.","journal-title":"J Psychiatr Res"},{"key":"649_CR13","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","volume":"343","author":"JP Higgins","year":"2011","unstructured":"Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.","journal-title":"BMJ"},{"key":"649_CR14","first-page":"CD004514","volume":"4","author":"M Malouf","year":"2003","unstructured":"Malouf M, Grimley EJ, Areosa SA. Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;4:CD004514.","journal-title":"Cochrane Database Syst Rev."},{"key":"649_CR15","doi-asserted-by":"crossref","unstructured":"Malouf R, Areosa Sastre A. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;3:CD004326.","DOI":"10.1002\/14651858.CD004394"},{"key":"649_CR16","doi-asserted-by":"crossref","unstructured":"Malouf R, Grimley Evans J. The effect of vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;4:CD004393.","DOI":"10.1002\/14651858.CD004393"},{"key":"649_CR17","doi-asserted-by":"crossref","unstructured":"Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;(4):CD004514.","DOI":"10.1002\/14651858.CD004514.pub2"},{"issue":"6","key":"649_CR18","doi-asserted-by":"publisher","first-page":"522.e2","DOI":"10.1016\/j.amjmed.2010.01.017","volume":"123","author":"DS Wald","year":"2010","unstructured":"Wald DS, Kasturiratne A, Simmonds M. Effect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trials. Am J Med. 2010;123(6):522.e2\u2013527.e2.","journal-title":"Am J Med"},{"issue":"9557","key":"649_CR19","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/S0140-6736(07)60109-3","volume":"369","author":"J Durga","year":"2007","unstructured":"Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369(9557):208\u201316.","journal-title":"Lancet"},{"issue":"2","key":"649_CR20","doi-asserted-by":"publisher","first-page":"657","DOI":"10.3945\/ajcn.113.076349","volume":"100","author":"R Clarke","year":"2014","unstructured":"Clarke R, Bennett D, Parish S, et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am J Clin Nutr. 2014;100(2):657\u201366.","journal-title":"Am J Clin Nutr"},{"issue":"9","key":"649_CR21","first-page":"844","volume":"11","author":"MM Li","year":"2014","unstructured":"Li MM, Yu JT, Wang HF, et al. Efficacy of vitamins B supplementation on mild cognitive impairment and Alzheimer\u2019s disease: a systematic review and meta-analysis. Curr Alzheimer Res. 2014;11(9):844\u201352.","journal-title":"Curr Alzheimer Res"},{"issue":"1","key":"649_CR22","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1177\/0891988716673466","volume":"30","author":"DM Zhang","year":"2017","unstructured":"Zhang DM, Ye JX, Mu JS, Cui XP. Efficacy of vtamin B supplementation on cognition in elderly patients with cognitive-related diseases. J Geriatr Psychiatry Neurol. 2017;30(1):50\u20139.","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"649_CR23","doi-asserted-by":"publisher","unstructured":"Enderami A, Zarghami M, Darvishi-Khezri H. The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review. Neurol Sci. 2018. \n                    https:\/\/doi.org\/10.1007\/s10072-018-3473-4\n                    \n                  \n                           (Epub ahead of print).","DOI":"10.1007\/s10072-018-3473-4"},{"issue":"8","key":"649_CR24","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1161\/STROKEAHA.113.001886","volume":"44","author":"GJ Hankey","year":"2013","unstructured":"Hankey GJ, Ford AH, Yi Q, et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013;44(8):2232\u20139.","journal-title":"Stroke"},{"issue":"15","key":"649_CR25","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1001\/jama.300.15.1774","volume":"300","author":"PS Aisen","year":"2008","unstructured":"Aisen PS, Schneider LS, Sano M, et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300(15):1774\u201383.","journal-title":"JAMA"},{"issue":"1","key":"649_CR26","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1046\/j.1365-2796.2003.01154.x","volume":"254","author":"R Clarke","year":"2003","unstructured":"Clarke R, Harrison G, Richards S. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med. 2003;254(1):67\u201375.","journal-title":"J Intern Med."},{"issue":"2","key":"649_CR27","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/gps.1856","volume":"23","author":"PJ Connelly","year":"2008","unstructured":"Connelly PJ, Prentice NP, Cousland G, Bonham J. A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer\u2019s disease. Int J Geriatr Psychiatry. 2008;23(2):155\u201360.","journal-title":"Int J Geriatr Psychiatry."},{"issue":"3","key":"649_CR28","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.clnu.2010.12.004","volume":"30","author":"T Kwok","year":"2011","unstructured":"Kwok T, Lee J, Law CB, et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin Nutr. 2011;30(3):297\u2013302.","journal-title":"Clin Nutr"},{"issue":"3","key":"649_CR29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1177\/0891988703256052","volume":"16","author":"BR Sommer","year":"2003","unstructured":"Sommer BR, Hoff AL, Costa M. Folic acid supplementation in dementia: a preliminary report. J Geriatr Psychiatry Neurol. 2003;16(3):156\u20139.","journal-title":"J Geriatr Psychiatry Neurol"},{"issue":"1","key":"649_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0167-4943(97)00028-9","volume":"26","author":"M Fioravanti","year":"1998","unstructured":"Fioravanti M, Ferrario E, Massaia M, et al. Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. Arch Gerontol Geriatr. 1998;26(1):1\u201313.","journal-title":"Arch Gerontol Geriatr"},{"issue":"6","key":"649_CR31","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1002\/gps.2758","volume":"27","author":"CA Jager de","year":"2012","unstructured":"de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27(6):592\u2013600.","journal-title":"Int J Geriatr Psychiatry."},{"key":"649_CR32","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.jns.2017.05.061","volume":"379","author":"SKS Ting","year":"2017","unstructured":"Ting SKS, Earnest A, Li H, et al. B vitamins and cognition in subjects with small vessel disease: a substudy of VITATOPS, a randomized, placebo-controlled trial. J Neurol Sci. 2017;379:124\u20136.","journal-title":"J Neurol Sci"},{"issue":"5","key":"649_CR33","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1136\/bjsm.2007.044735","volume":"42","author":"JG Uffelen van","year":"2008","unstructured":"van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med. 2008;42(5):344\u201351.","journal-title":"Br J Sports Med"},{"issue":"6","key":"649_CR34","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1093\/jn\/132.6.1345","volume":"132","author":"J Bryan","year":"2002","unstructured":"Bryan J, Calvaresi E, Hughes D. Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr. 2002;132(6):1345\u201356.","journal-title":"J Nutr"},{"issue":"10","key":"649_CR35","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1179\/1476830514Y.0000000136","volume":"19","author":"D Cheng","year":"2016","unstructured":"Cheng D, Kong H, Pang W, et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia. Nutr Neurosci. 2016;19(10):461\u20136.","journal-title":"Nutr Neurosci."},{"issue":"4","key":"649_CR36","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/BF02247729","volume":"109","author":"JB Deijen","year":"1992","unstructured":"Deijen JB, van der Beek EJ, Orlebeke JF, van den Berg H. Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology. 1992;109(4):489\u201396.","journal-title":"Psychopharmacology"},{"issue":"2","key":"649_CR37","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1093\/ajcn\/84.2.361","volume":"84","author":"SJ Eussen","year":"2006","unstructured":"Eussen SJ, de Groot LC, Joosten LW, et al. Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Am J Clin Nutr. 2006;84(2):361\u201370.","journal-title":"Am J Clin Nutr"},{"issue":"17","key":"649_CR38","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1212\/WNL.0b013e3181f962c4","volume":"75","author":"AH Ford","year":"2010","unstructured":"Ford AH, Flicker L, Alfonso H, et al. Vitamins B(12), B(6), and folic acid for cognition in older men. Neurology. 2010;75(17):1540\u20137.","journal-title":"Neurology."},{"issue":"3","key":"649_CR39","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/S0165-0327(03)00169-1","volume":"81","author":"AM Hvas","year":"2004","unstructured":"Hvas AM, Juul S, Lauritzen L, Nexo E, Ellegaard J. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004;81(3):269\u201373.","journal-title":"J Affect Disord"},{"issue":"6","key":"649_CR40","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.3945\/ajcn.2008.26404","volume":"88","author":"JH Kang","year":"2008","unstructured":"Kang JH, Cook N, Manson J, et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr. 2008;88(6):1602\u201310.","journal-title":"Am J Clin Nutr"},{"issue":"5","key":"649_CR41","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1093\/ajcn\/81.5.1155","volume":"81","author":"C Lewerin","year":"2005","unstructured":"Lewerin C, Matousek M, Steen G, et al. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr. 2005;81(5):1155\u201362.","journal-title":"Am J Clin Nutr"},{"issue":"26","key":"649_CR42","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1056\/NEJMoa054025","volume":"354","author":"JA McMahon","year":"2006","unstructured":"McMahon JA, Green TJ, Skeaff CM, et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354(26):2764\u201372.","journal-title":"N Engl J Med"},{"issue":"1","key":"649_CR43","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.archger.2005.10.002","volume":"43","author":"R Pathansali","year":"2006","unstructured":"Pathansali R, Mangoni AA, Creagh-Brown B, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr. 2006;43(1):127\u201337.","journal-title":"Arch Gerontol Geriatr"},{"issue":"1","key":"649_CR44","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3945\/ajcn.110.007799","volume":"95","author":"JG Walker","year":"2012","unstructured":"Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms: the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95(1):194\u2013203.","journal-title":"Am J Clin Nutr"},{"key":"649_CR45","doi-asserted-by":"crossref","unstructured":"Andreeva VA, Kesse-Guyot E, Barberger-Gateau P, et al. Cognitive function after supplementation with B vitamins and long-chain omega-3 fatty acids: ancillary findings from the SU.FOL.OM3 randomized trial. Am J Clin Nutr. 2011;94(1):278\u201386.","DOI":"10.3945\/ajcn.110.006320"},{"issue":"3","key":"649_CR46","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1053\/j.ajkd.2009.05.013","volume":"54","author":"CB Brady","year":"2009","unstructured":"Brady CB, Gaziano JM, Cxypoliski RA, et al. Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study. Am J Kidney Dis. 2009;54(3):440\u20139.","journal-title":"Am J Kidney Dis"},{"issue":"3","key":"649_CR47","doi-asserted-by":"publisher","first-page":"639","DOI":"10.3945\/ajcn.115.110775","volume":"102","author":"AD Dangour","year":"2015","unstructured":"Dangour AD, Allen E, Clarke R, et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. Am J Clin Nutr. 2015;102(3):639\u201347.","journal-title":"Am J Clin Nutr"},{"issue":"6","key":"649_CR48","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/j.clnu.2016.10.018","volume":"36","author":"T Kwok","year":"2017","unstructured":"Kwok T, Lee J, Ma RC, et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clin Nutr. 2017;36(6):1509\u201315.","journal-title":"Clin Nutr"},{"issue":"15","key":"649_CR49","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1056\/NEJMoa060900","volume":"354","author":"E Lonn","year":"2006","unstructured":"Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354(15):1567\u201377.","journal-title":"N Engl J Med"},{"issue":"1","key":"649_CR50","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1046\/j.1532-5415.2002.50020.x","volume":"50","author":"EC Seal","year":"2002","unstructured":"Seal EC, Metz J, Flicker L, Melny J. A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. J Am Geriatr Soc. 2002;50(1):146\u201351.","journal-title":"J Am Geriatr Soc"},{"issue":"6","key":"649_CR51","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1093\/ajcn\/82.6.1320","volume":"82","author":"DJ Stott","year":"2005","unstructured":"Stott DJ, MacIntosh G, Lowe GD, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82(6):1320\u20136.","journal-title":"Am J Clin Nutr"},{"key":"649_CR52","doi-asserted-by":"crossref","unstructured":"Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303(24):2486\u201394.","DOI":"10.1001\/jama.2010.840"},{"issue":"8","key":"649_CR53","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1111\/j.1532-5415.2004.52379_10.x","volume":"52","author":"A Garcia","year":"2004","unstructured":"Garcia A, Pulman K, Zanibbi K, et al. Cobalamin reduces homocysteine in older adults on folic acid-fortified diet: a pilot, double-blind, randomized, placebo-controlled trial. J Am Geriatr Soc. 2004;52(8):1410\u20132.","journal-title":"J Am Geriatr Soc"},{"key":"649_CR54","first-page":"295","volume":"58","author":"AB Hill","year":"1965","unstructured":"Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295\u2013300.","journal-title":"Proc R Soc Med."},{"issue":"2","key":"649_CR55","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3233\/JAD-171042","volume":"62","author":"AD Smith","year":"2018","unstructured":"Smith AD, Refsum H, Bottiglieri T, et al. Homocysteine and dementia: an international consensus statement. J Alzheimers Dis. 2018;62(2):561\u201370.","journal-title":"J Alzheimers Dis."},{"issue":"9","key":"649_CR56","doi-asserted-by":"publisher","first-page":"e12244","DOI":"10.1371\/journal.pone.0012244","volume":"5","author":"AD Smith","year":"2010","unstructured":"Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244.","journal-title":"PLoS One"},{"issue":"9","key":"649_CR57","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/S1474-4422(10)70187-3","volume":"9","author":"Group VTS","year":"2010","unstructured":"Group VTS. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol. 2010;9(9):855\u201365.","journal-title":"Lancet Neurol."},{"issue":"13","key":"649_CR58","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1016\/j.febslet.2006.04.088","volume":"580","author":"R Obeid","year":"2006","unstructured":"Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580(13):2994\u20133005.","journal-title":"FEBS Lett"},{"issue":"1\u20133","key":"649_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-5793(02)02702-3","volume":"518","author":"SB Vafai","year":"2002","unstructured":"Vafai SB, Stock JB. Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer\u2019s disease. FEBS Lett. 2002;518(1\u20133):1\u20134.","journal-title":"FEBS Lett"},{"issue":"15","key":"649_CR60","doi-asserted-by":"publisher","first-page":"12915","DOI":"10.1074\/jbc.M112372200","volume":"277","author":"X Sai","year":"2002","unstructured":"Sai X, Kawamura Y, Kokame K, et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem. 2002;277(15):12915\u201320.","journal-title":"J Biol Chem"},{"issue":"1","key":"649_CR61","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/S0014-5793(00)01278-3","volume":"470","author":"D Xu","year":"2000","unstructured":"Xu D, Neville R, Finkel T. Homocysteine accelerates endothelial cell senescence. FEBS Lett. 2000;470(1):20\u20134.","journal-title":"FEBS Lett"},{"issue":"2","key":"649_CR62","first-page":"269","volume":"123","author":"N Orentreich","year":"1993","unstructured":"Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span. J Nutr. 1993;123(2):269\u201374.","journal-title":"J Nutr"},{"key":"649_CR63","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1146\/annurev-nutr-071715-050947","volume":"36","author":"AD Smith","year":"2016","unstructured":"Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211\u201339.","journal-title":"Annu Rev Nutr"},{"issue":"7","key":"649_CR64","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/JGP.0b013e3181f17eed","volume":"19","author":"RC Ho","year":"2011","unstructured":"Ho RC, Cheung MW, Fu E, et al. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Am J Geriatr Psychiatry. 2011;19(7):607\u201317.","journal-title":"Am J Geriatr Psychiatry."},{"issue":"1","key":"649_CR65","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/ng0595-111","volume":"10","author":"P Frosst","year":"1995","unstructured":"Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111\u20133.","journal-title":"Nat Genet"},{"issue":"1","key":"649_CR66","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1136\/jnnp.2011.242446","volume":"83","author":"AH Ford","year":"2012","unstructured":"Ford AH, Flicker L, Alfonso H, et al. Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia. J Neurol Neurosurg Psychiatry. 2012;83(1):70\u20135.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"2","key":"649_CR67","doi-asserted-by":"publisher","first-page":"747","DOI":"10.3233\/JAD-150977","volume":"52","author":"Q Hu","year":"2016","unstructured":"Hu Q, Teng W, Li J, Hao F, Wang N. Homocysteine and Alzheimer\u2019s disease: evidence for a causal link from Mendelian randomization. J Alzheimers Dis. 2016;52(2):747\u201356.","journal-title":"J Alzheimers Dis."},{"issue":"9791","key":"649_CR68","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/S0140-6736(11)60872-6","volume":"378","author":"MV Holmes","year":"2011","unstructured":"Holmes MV, Newcombe P, Hubacek JA, et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet. 2011;378(9791):584\u201394.","journal-title":"Lancet"}],"container-title":["Drugs &amp; Aging"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40266-019-00649-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40266-019-00649-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40266-019-00649-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T23:06:10Z","timestamp":1585868770000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40266-019-00649-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,4]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["649"],"URL":"https:\/\/doi.org\/10.1007\/s40266-019-00649-w","relation":{},"ISSN":["1170-229X","1179-1969"],"issn-type":[{"value":"1170-229X","type":"print"},{"value":"1179-1969","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,4]]},"assertion":[{"value":"4 April 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"No sources of funding were received for the preparation of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Andrew H. Ford and Osvaldo P. Almeida have no conflicts that are directly relevant to the content of this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}