{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:36:22Z","timestamp":1790854582403,"version":"4.1.0"},"reference-count":61,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":6054,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Clinical Nutrition"],"published-print":{"date-parts":[[2006,8]]},"DOI":"10.1093\/ajcn\/84.2.361","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T07:02:49Z","timestamp":1519282969000},"page":"361-370","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":180,"title":["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"],"prefix":"10.1016","volume":"84","author":[{"given":"Simone J","family":"Eussen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette C","family":"de Groot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth W","family":"Joosten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubia J","family":"Bloo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per M","family":"Ueland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Schneede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk J","family":"Blom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willibrord H","family":"Hoefnagels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wija A","family":"van Staveren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1093\/ajcn\/84.2.361_bib1","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/ajcn\/77.5.1241","article-title":"Screening for vitamin B-12 and folate deficiency in older persons","volume":"77","author":"Clarke","year":"2003","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1093\/ageing\/afg109","article-title":"Vitamin B12 and folate deficiency in later life","volume":"33","author":"Clarke","year":"2004","journal-title":"Age Ageing"},{"key":"10.1093\/ajcn\/84.2.361_bib3","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.nutr.19.1.357","article-title":"Vitamin B12 deficiency in the elderly","volume":"19","author":"Baik","year":"1999","journal-title":"Annu Rev Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib4","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0268-960X(89)90028-3","article-title":"Cobalamin-folate interrelations","volume":"3","author":"Chanarin","year":"1989","journal-title":"Blood Rev"},{"key":"10.1093\/ajcn\/84.2.361_bib5","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1212\/WNL.45.8.1435","article-title":"Current concepts in the diagnosis of cobalamin deficiency","volume":"45","author":"Green","year":"1995","journal-title":"Neurology"},{"key":"10.1093\/ajcn\/84.2.361_bib6","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1056\/NEJM198806303182604","article-title":"Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis","volume":"318","author":"Lindenbaum","year":"1988","journal-title":"N Engl J Med"},{"key":"10.1093\/ajcn\/84.2.361_bib7","series-title":"Chemistry and biochemistry of B12.","article-title":"B12 and nutrition","author":"Stabler","year":"2000"},{"key":"10.1093\/ajcn\/84.2.361_bib8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/00005792-199107000-00001","article-title":"Neurologic aspects of cobalamin deficiency","volume":"70","author":"Healton","year":"1991","journal-title":"Medcine (Baltimore)"},{"key":"10.1093\/ajcn\/84.2.361_bib9","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1532-5415.1992.tb01939.x","article-title":"Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study","volume":"40","author":"Martin","year":"1992","journal-title":"J Am Geriatr Soc"},{"key":"10.1093\/ajcn\/84.2.361_bib10","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1365-2796.2004.01437.x","article-title":"Holotranscobalamin\u2014a first choice assay for diagnosing early vitamin B deficiency","volume":"257","author":"Hvas","year":"2005","journal-title":"J Intern Med"},{"key":"10.1093\/ajcn\/84.2.361_bib11","first-page":"33","article-title":"Neuropsychiatric consequences of cobalamin deficiency","volume":"36","author":"Beck","year":"1991","journal-title":"Adv Intern Med"},{"key":"10.1093\/ajcn\/84.2.361_bib12","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/ajcn\/66.4.750","article-title":"Cobalamin, the stomach, and aging","volume":"66","author":"Carmel","year":"1997","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib13","doi-asserted-by":"crossref","first-page":"614S","DOI":"10.1093\/ajcn\/71.2.614s","article-title":"B vitamins, homocysteine, and neurocognitive function in the elderly","volume":"71","author":"Selhub","year":"2000","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib14","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/geronb\/56.6.P327","article-title":"B vitamins, cognition, and aging: a review","volume":"56","author":"Calvaresi","year":"2001","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"10.1093\/ajcn\/84.2.361_bib15","article-title":"Vitamin B12 for cognition","author":"Malouf","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1093\/ajcn\/84.2.361_bib16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1017\/S1041610295001876","article-title":"Vitamin B12 deficiency and dementia","volume":"7","author":"Cunha","year":"1995","journal-title":"Int Psychogeriatr"},{"key":"10.1093\/ajcn\/84.2.361_bib17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1007\/BF00886874","article-title":"Dementia and subnormal levels of vitamin B12: effects of replacement therapy on dementia","volume":"243","author":"Teunisse","year":"1996","journal-title":"J Neurol"},{"key":"10.1093\/ajcn\/84.2.361_bib18","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/(SICI)1099-1166(199809)13:9<611::AID-GPS832>3.0.CO;2-O","article-title":"Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels","volume":"13","author":"Kwok","year":"1998","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.1093\/ajcn\/84.2.361_bib19","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/(SICI)1099-1166(200003)15:3<226::AID-GPS98>3.0.CO;2-K","article-title":"Vitamin B12 deficiency in dementia and cognitive impairment: the effects of treatment on neuropsychological function","volume":"15","author":"Eastley","year":"2000","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.1093\/ajcn\/84.2.361_bib20","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/gps.388","article-title":"Improvement of cognitive functions after cobalamin\/folate supplementation in elderly patients with dementia and elevated plasma homocysteine","volume":"16","author":"Nilsson","year":"2001","journal-title":"Int J Geriatr Psychiatry"},{"key":"10.1093\/ajcn\/84.2.361_bib21","doi-asserted-by":"crossref","first-page":"M775","DOI":"10.1093\/gerona\/56.12.M775","article-title":"Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons","volume":"56","author":"van Asselt","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.1093\/ajcn\/84.2.361_bib22","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/0891988704272308","article-title":"Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects","volume":"18","author":"Osimani","year":"2005","journal-title":"J Geriatr Psychiatry Neurol"},{"key":"10.1093\/ajcn\/84.2.361_bib23","first-page":"133","article-title":"Vitamin B12 deficiency and dementia: a multicenter epidemiologic and therapeutic study preliminary therapeutic trial","volume":"73","author":"De La Fourniere","year":"1997","journal-title":"Sem des Hopitaux"},{"key":"10.1093\/ajcn\/84.2.361_bib24","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1532-5415.2002.50020.x","article-title":"A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations","volume":"50","author":"Seal","year":"2002","journal-title":"J Am Geriatr Soc"},{"key":"10.1093\/ajcn\/84.2.361_bib25","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0165-0327(03)00169-1","article-title":"No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study","volume":"81","author":"Hvas","year":"2004","journal-title":"J Affect Disord"},{"key":"10.1093\/ajcn\/84.2.361_bib26","first-page":"254","article-title":"Prevalence of vitamin B12 deficiency among demented patients and cognitive recovery with cobalamin replacement","volume":"6","author":"Abyad","year":"2002","journal-title":"J Nutr Health Aging"},{"key":"10.1093\/ajcn\/84.2.361_bib27","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/ageing\/24.6.536","article-title":"Review: cobalamin deficiency and mental impairment in elderly people","volume":"24","author":"van-Goor","year":"1995","journal-title":"Age Ageing"},{"key":"10.1093\/ajcn\/84.2.361_bib28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1001\/archinte.165.10.1167","article-title":"Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial","volume":"165","author":"Eussen","year":"2005","journal-title":"Arch Intern Med"},{"key":"10.1093\/ajcn\/84.2.361_bib29","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jclinepi.2003.08.015","article-title":"A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults","volume":"57","author":"Valuck","year":"2004","journal-title":"J Clin Epidemiol"},{"key":"10.1093\/ajcn\/84.2.361_bib30","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1093\/ajcn\/77.5.1318","article-title":"Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study","volume":"77","author":"van Oort","year":"2003","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib31","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/ajcn\/73.2.338","article-title":"Nutrient-dense foods and exercise in frail elderly: effects on B vitamins, homocysteine, methylmalonic acid, and neuropsychological functioning","volume":"73","author":"de Jong","year":"2001","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2165\/00002512-199507060-00006","article-title":"Cognitive impairment in elderly people. Predisposing factors and implications for experimental drug studies","volume":"7","author":"Jolles","year":"1995","journal-title":"Drugs Aging"},{"key":"10.1093\/ajcn\/84.2.361_bib33","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1373\/clinchem.2005.053835","article-title":"Automated assay for the determination of methylmalonic acid, total homocysteine, and related amino acids in human serum or plasma by means of methylchloroformate derivatization and gas chromatography-mass spectrometry","volume":"51","author":"Windelberg","year":"2005","journal-title":"Clin Chem"},{"key":"10.1093\/ajcn\/84.2.361_bib34","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/clinchem\/48.3.526","article-title":"Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum","volume":"48","author":"Ulleland","year":"2002","journal-title":"Clin Chem"},{"key":"10.1093\/ajcn\/84.2.361_bib35","unstructured":"Immulite 2000 Vitamin B12. Internet: http:\/\/www.dpcweb.com\/package_inserts\/immulite_2000\/pdfs\/Anemia\/l2kvb-161.pdf (accessed 14 May 2003)."},{"key":"10.1093\/ajcn\/84.2.361_bib36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"10.1093\/ajcn\/84.2.361_bib37","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1001\/archneur.58.12.1985","article-title":"Current concepts in mild cognitive impairment","volume":"58","author":"Petersen","year":"2001","journal-title":"Arch Neurol"},{"key":"10.1093\/ajcn\/84.2.361_bib38","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and validation of a geriatric depression screening scale: a preliminary report","volume":"17","author":"Yesavage","year":"1983","journal-title":"J Psychiatr Res"},{"key":"10.1093\/ajcn\/84.2.361_bib39","series-title":"Cognitive aging and health-related factors.","first-page":"113","author":"Houx","year":"1991"},{"key":"10.1093\/ajcn\/84.2.361_bib40","series-title":"Manual of the Complex Figure Test.","author":"Visser","year":"1985"},{"key":"10.1093\/ajcn\/84.2.361_bib41","series-title":"De nieuwe 15-woordentest (A en B) een handleiding. (New 15-words test (A and B) a manual).","author":"Saan","year":"1986"},{"key":"10.1093\/ajcn\/84.2.361_bib42","doi-asserted-by":"crossref","first-page":"271","DOI":"10.2466\/pms.1958.8.3.271","article-title":"Validity of the Trail Making Test as an indicator of organic brain damage","volume":"8","author":"Reitan","year":"1958","journal-title":"Percept Mot Skills"},{"key":"10.1093\/ajcn\/84.2.361_bib43","series-title":"Wechsler Memory Scale\u2014revised manual.","author":"Wechsler","year":"1987"},{"key":"10.1093\/ajcn\/84.2.361_bib44","series-title":"Guide to using the Coloured Progressive Matrices.","author":"Raven","year":"1965"},{"key":"10.1093\/ajcn\/84.2.361_bib45","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1037\/h0054651","article-title":"Studies of interference in serial verbal reactions","volume":"18","author":"Stroop","year":"1935","journal-title":"J Exp Psychol"},{"key":"10.1093\/ajcn\/84.2.361_bib46","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1080\/03610739308253934","article-title":"Stroop interference: aging effects assessed with the Stroop Color-Word Test","volume":"19","author":"Houx","year":"1993","journal-title":"Exp Aging Res"},{"key":"10.1093\/ajcn\/84.2.361_bib47","series-title":"Manual for the Wechsler Adult Intelligence Scale\u2014revised.","author":"Wechsler","year":"1981"},{"key":"10.1093\/ajcn\/84.2.361_bib48","series-title":"Handleiding Groninger Intelligentietest. (Manual Groningen Intelligence Test.)","year":"1983"},{"key":"10.1093\/ajcn\/84.2.361_bib49","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1001\/archneur.56.3.303","article-title":"Mild cognitive impairment: clinical characterization and outcome","volume":"56","author":"Petersen","year":"1999","journal-title":"Arch Neurol"},{"key":"10.1093\/ajcn\/84.2.361_bib50","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1037\/0033-2909.117.2.285","article-title":"Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity","volume":"117","author":"Burt","year":"1995","journal-title":"Psychol Bull"},{"key":"10.1093\/ajcn\/84.2.361_bib51","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3102\/10769986023004323","article-title":"Using SAS PROC MIXED to fit multilevel models, hierarchical models, and individual growth models","volume":"24","author":"Singer","year":"1998","journal-title":"J Educ Behav Stat"},{"key":"10.1093\/ajcn\/84.2.361_bib52","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/ajcn\/46.3.387","article-title":"Nutrition science as a continually unfolding story: the folate and vitamin B-12 paradigm","volume":"46","author":"Herbert","year":"1987","journal-title":"Am J Clin Nutr"},{"key":"10.1093\/ajcn\/84.2.361_bib53","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD004514","article-title":"Folic acid with or without vitamin B12 for cognition and dementia","author":"Malouf","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"10.1093\/ajcn\/84.2.361_bib54","series-title":"Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline.","year":"1998"},{"key":"10.1093\/ajcn\/84.2.361_bib55","unstructured":"Scientific Committee on Food Opinion of the Scientific Committee on Food on the tolerable upper intake level of vitamin B12. Internet: http:\/\/ec.europa.eu\/comm\/food\/fs\/sc\/scf\/out80d_en.pdf (accessed 29 May 2006)."},{"key":"10.1093\/ajcn\/84.2.361_bib56","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4065\/77.3.291","article-title":"Reversible myelopathy in a 34-year-old man with vitamin B12 deficiency","volume":"77","author":"Pittock","year":"2002","journal-title":"Mayo Clin Proc"},{"key":"10.1093\/ajcn\/84.2.361_bib57","series-title":"Amyloid protein precursor in development, aging and Alzheimer Disease.","first-page":"1","author":"Masters","year":"1994"},{"key":"10.1093\/ajcn\/84.2.361_bib58","doi-asserted-by":"crossref","first-page":"476","DOI":"10.7326\/0003-4819-109-6-476","article-title":"The reversible dementias: do they reverse","volume":"109","author":"Clarfield","year":"1988","journal-title":"Ann Intern Med"},{"key":"10.1093\/ajcn\/84.2.361_bib59","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/jnr.10416","article-title":"Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage","volume":"70","author":"Ho","year":"2002","journal-title":"J Neurosci Res"},{"key":"10.1093\/ajcn\/84.2.361_bib60","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000071002","article-title":"Vitamin B12\u2013B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment","volume":"16","author":"Lehmann","year":"2003","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10.1093\/ajcn\/84.2.361_bib61","first-page":"234","article-title":"Homocysteine metabolism: nutritional modulation and impact on health and disease","volume":"2","author":"Miller","year":"1997","journal-title":"Altern Med Rev"}],"container-title":["The American Journal of Clinical Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002916523290188?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002916523290188?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/ajcn\/article-pdf\/84\/2\/361\/24142791\/znu00806000361.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T12:52:45Z","timestamp":1685191965000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002916523290188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,8]]},"references-count":61,"aliases":["10.1093\/ajcn\/84.1.361","10.1093\/ajcn\/84.1.361"],"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,8]]}},"alternative-id":["S0002916523290188"],"URL":"https:\/\/doi.org\/10.1093\/ajcn\/84.2.361","relation":{},"ISSN":["0002-9165"],"issn-type":[{"value":"0002-9165","type":"print"}],"subject":[],"published":{"date-parts":[[2006,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"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","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Clinical Nutrition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1093\/ajcn\/84.2.361","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2006 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}