{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:06:08Z","timestamp":1786982768423,"version":"build-2736575974"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.5"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Drugs"],"published-print":{"date-parts":[[2013,6]]},"DOI":"10.1007\/s40263-013-0077-7","type":"journal-article","created":{"date-parts":[[2013,6,3]],"date-time":"2013-06-03T02:23:40Z","timestamp":1370226220000},"page":"469-478","source":"Crossref","is-referenced-by-count":135,"title":["The Safety, Tolerability, and Efficacy of Once-Daily Memantine (28\u00a0mg): A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients with Moderate-to-Severe Alzheimer\u2019s Disease Taking Cholinesterase Inhibitors"],"prefix":"10.1007","volume":"27","author":[{"given":"George T.","family":"Grossberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo","family":"Manes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo F.","family":"Allegri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Miguel","family":"Guti\u00e9rrez-Robledo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Gloger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. Daniel","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vojislav","family":"Pejovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Perhach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,6,4]]},"reference":[{"issue":"11","key":"77_CR1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1111\/j.1525-1497.2001.10123.x","volume":"16","author":"KM Langa","year":"2001","unstructured":"Langa KM, Chernew ME, Kabeto MU, Herzog AR, Ofstedal MB, Willis RJ, et al. National estimates of the quantity and cost of informal caregiving for the elderly with dementia. J Gen Intern Med. 2001;16(11):770\u20138.","journal-title":"J Gen Intern Med"},{"issue":"10","key":"77_CR2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1097\/JGP.0b013e3181d5745d","volume":"18","author":"S Mohamed","year":"2010","unstructured":"Mohamed S, Rosenheck R, Lyketsos CG, Schneider LS. Caregiver burden in Alzheimer disease: cross-sectional and longitudinal patient correlates. Am J Geriatr Psychiatry. 2010;18(10):917\u201327.","journal-title":"Am J Geriatr Psychiatry"},{"issue":"12","key":"77_CR3","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1177\/070674371005501204","volume":"55","author":"N Herrmann","year":"2010","unstructured":"Herrmann N, Tam DY, Balshaw R, Sambrook R, Lesnikova N, Lanctot KL. The relation between disease severity and cost of caring for patients with Alzheimer disease in Canada. Can J Psychiatry. 2010;55(12):768\u201375.","journal-title":"Can J Psychiatry"},{"issue":"2","key":"77_CR4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1046\/j.1532-5415.2002.50065.x","volume":"50","author":"GW Small","year":"2002","unstructured":"Small GW, McDonnell DD, Brooks RL, Papadopoulos G. The impact of symptom severity on the cost of Alzheimer\u2019s disease. J Am Geriatr Soc. 2002;50(2):321\u20137.","journal-title":"J Am Geriatr Soc"},{"issue":"12","key":"77_CR5","doi-asserted-by":"crossref","first-page":"793","DOI":"10.2165\/00002512-200421120-00004","volume":"21","author":"CM Hughes","year":"2004","unstructured":"Hughes CM. Medication non-adherence in the elderly: how big is the problem? Drugs Aging. 2004;21(12):793\u2013811.","journal-title":"Drugs Aging"},{"issue":"5","key":"77_CR6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1056\/NEJMra050100","volume":"353","author":"L Osterberg","year":"2005","unstructured":"Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487\u201397.","journal-title":"N Engl J Med"},{"issue":"11","key":"77_CR7","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1185\/030079907X233403","volume":"23","author":"G Small","year":"2007","unstructured":"Small G, Dubois B. A review of compliance to treatment in Alzheimer\u2019s disease: potential benefits of a transdermal patch. Curr Med Res Opin. 2007;23(11):2705\u201313.","journal-title":"Curr Med Res Opin"},{"issue":"14","key":"77_CR8","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1056\/NEJMoa013128","volume":"348","author":"B Reisberg","year":"2003","unstructured":"Reisberg B, Doody R, St\u00f6ffler A, Schmitt F, Ferris S, M\u00f6bius HJ. Memantine in moderate-to-severe Alzheimer\u2019s disease. N Engl J Med. 2003;348(14):1333\u201341.","journal-title":"N Engl J Med"},{"issue":"3","key":"77_CR9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/jama.291.3.317","volume":"291","author":"PN Tariot","year":"2004","unstructured":"Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317\u201324.","journal-title":"JAMA"},{"key":"77_CR10","doi-asserted-by":"crossref","unstructured":"McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006(2):CD003154.","DOI":"10.1002\/14651858.CD003154.pub5"},{"issue":"7","key":"77_CR11","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2165\/00002018-200831070-00003","volume":"31","author":"MR Farlow","year":"2008","unstructured":"Farlow MR, Graham SM, Alva G. Memantine for the treatment of Alzheimer\u2019s disease: tolerability and safety data from clinical trials. Drug Saf. 2008;31(7):577\u201385.","journal-title":"Drug Saf"},{"key":"77_CR12","unstructured":"Namenda\u00ae U.S. Prescribing Information. St. Louis: Forest Pharmaceuticals, Inc.; 2007."},{"issue":"11","key":"77_CR13","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/S0027-9684(15)31515-7","volume":"100","author":"OL Lopez","year":"2008","unstructured":"Lopez OL, Mackell JA, Sun Y, Kassalow LM, Xu Y, McRae T, et al. Effectiveness and safety of donepezil in Hispanic patients with Alzheimer\u2019s disease: a 12-week open-label study. J Natl Med Assoc. 2008;100(11):1350\u20138.","journal-title":"J Natl Med Assoc"},{"key":"77_CR14","volume-title":"Diagnostic and statistical manual of mental disorders: DSM-IV-TR","author":"American Psychiatric Association Task Force on DSM-IV","year":"2000","unstructured":"American Psychiatric Association Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed. Washington, DC: American Psychiatric Association; 2000.","edition":"4"},{"key":"77_CR15","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1212\/WNL.34.7.939","volume":"34","author":"G McKhann","year":"1984","unstructured":"McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer\u2019s disease: report of the NINCDS\u2013ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer\u2019s Disease. Neurology. 1984;34:939\u201344.","journal-title":"Neurology"},{"issue":"3","key":"77_CR16","doi-asserted-by":"crossref","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"},{"issue":"1","key":"77_CR17","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1001\/archneur.1994.00540130067012","volume":"51","author":"M Panisset","year":"1994","unstructured":"Panisset M, Roudier M, Saxton J, Boller F. Severe impairment battery. A neuropsychological test for severely demented patients. Arch Neurol. 1994;51(1):41\u20135.","journal-title":"Arch Neurol"},{"issue":"Suppl 2","key":"77_CR18","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1097\/00002093-199700112-00004","volume":"11","author":"LS Schneider","year":"1997","unstructured":"Schneider LS, Olin JT, Doody RS, Clark CM, Morris JC, Reisberg B, et al. Validity and reliability of the Alzheimer\u2019s Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer\u2019s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S22\u201332.","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"Suppl 2","key":"77_CR19","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1097\/00002093-199700112-00005","volume":"11","author":"D Galasko","year":"1997","unstructured":"Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer\u2019s disease. The Alzheimer\u2019s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(Suppl 2):S33\u20139.","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"4","key":"77_CR20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1017\/S1355617705050502","volume":"11","author":"D Galasko","year":"2005","unstructured":"Galasko D, Schmitt F, Thomas R, Jin S, Bennett D. Detailed assessment of activities of daily living in moderate to severe Alzheimer\u2019s disease. J Int Neuropsychol Soc. 2005;11(4):446\u201353.","journal-title":"J Int Neuropsychol Soc"},{"issue":"12","key":"77_CR21","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1212\/WNL.44.12.2308","volume":"44","author":"JL Cummings","year":"1994","unstructured":"Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308\u201314.","journal-title":"Neurology"},{"key":"77_CR22","volume-title":"A compendium of neuropsychological tests: administration, norms, and commentary","author":"E Strauss","year":"2006","unstructured":"Strauss E, Sherman EMS, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary. 3rd ed. Oxford: Oxford University Press; 2006.","edition":"3"},{"issue":"4","key":"77_CR23","first-page":"653","volume":"24","author":"B Reisberg","year":"1988","unstructured":"Reisberg B. Functional assessment staging (FAST). Psychopharmacol Bull. 1988;24(4):653\u20139.","journal-title":"Psychopharmacol Bull"},{"issue":"2","key":"77_CR24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/WAD.0b013e318065c495","volume":"21","author":"CH Dyck van","year":"2007","unstructured":"van Dyck CH, Tariot PN, Meyers B, Malca Resnick E. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21(2):136\u201343.","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"4","key":"77_CR25","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1159\/000254495","volume":"28","author":"E Gleichgerrcht","year":"2009","unstructured":"Gleichgerrcht E, Camino J, Roca M, Torralva T, Manes F. Assessment of functional impairment in dementia with the Spanish version of the Activities of Daily Living Questionnaire. Dement Geriatr Cogn Disord. 2009;28(4):380\u20138.","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"8","key":"77_CR26","first-page":"395","volume":"20","author":"J Olazaran","year":"2005","unstructured":"Olazaran J, Mouronte P, Bermejo F. Clinical validity of two scales of instrumental activities in Alzheimer\u2019s disease. Neurologia. 2005;20(8):395\u2013401.","journal-title":"Neurologia"},{"issue":"6","key":"77_CR27","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1159\/000228259","volume":"27","author":"G Sanchez-Benavides","year":"2009","unstructured":"Sanchez-Benavides G, Manero RM, Quinones-Ubeda S, de Sola S, Quintana M, Pena-Casanova J. Spanish version of the Bayer Activities of Daily Living scale in mild cognitive impairment and mild Alzheimer disease: discriminant and concurrent validity. Dement Geriatr Cogn Disord. 2009;27(6):572\u20138.","journal-title":"Dement Geriatr Cogn Disord"},{"issue":"4","key":"77_CR28","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/01.wad.0000213862.20108.f5","volume":"20","author":"M Sano","year":"2006","unstructured":"Sano M, Egelko S, Jin S, Cummings J, Clark CM, Pawluczyk S, et al. Spanish instrument protocol: new treatment efficacy instruments for Spanish-speaking patients in Alzheimer disease clinical trials. Alzheimer Dis Assoc Disord. 2006;20(4):232\u201341.","journal-title":"Alzheimer Dis Assoc Disord"},{"issue":"5","key":"77_CR29","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/gps.1341","volume":"20","author":"S Gauthier","year":"2005","unstructured":"Gauthier S, Wirth Y, Mobius HJ. Effects of memantine on behavioural symptoms in Alzheimer\u2019s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry. 2005;20(5):459\u201364.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"5","key":"77_CR30","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/gps.1949","volume":"23","author":"S Gauthier","year":"2008","unstructured":"Gauthier S, Loft H, Cummings J. Improvement in behavioural symptoms in patients with moderate to severe Alzheimer\u2019s disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry. 2008;23(5):537\u201345.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"3","key":"77_CR31","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4088\/JCP.v69n0302","volume":"69","author":"GK Wilcock","year":"2008","unstructured":"Wilcock GK, Ballard CG, Cooper JA, Loft H. Memantine for agitation\/aggression and psychosis in moderately severe to severe Alzheimer\u2019s disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008;69(3):341\u20138.","journal-title":"J Clin Psychiatry"},{"issue":"5","key":"77_CR32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1002\/(SICI)1099-1166(200005)15:5<393::AID-GPS120>3.0.CO;2-O","volume":"15","author":"DG Harwood","year":"2000","unstructured":"Harwood DG, Barker WW, Ownby RL, Duara R. Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer\u2019s disease. Int J Geriatr Psychiatry. 2000;15(5):393\u2013400.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"5","key":"77_CR33","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/gps.490","volume":"17","author":"MS Beeri","year":"2002","unstructured":"Beeri MS, Werner P, Davidson M, Noy S. The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer\u2019s disease patients. Int J Geriatr Psychiatry. 2002;17(5):403\u20138.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"Suppl 21","key":"77_CR34","first-page":"3","volume":"62","author":"SI Finkel","year":"2001","unstructured":"Finkel SI. Behavioral and psychological symptoms of dementia: a current focus for clinicians, researchers, and caregivers. J Clin Psychiatry. 2001;62(Suppl 21):3\u20136.","journal-title":"J Clin Psychiatry"},{"issue":"1","key":"77_CR35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1037\/0894-4105.22.1.17","volume":"22","author":"CM Ramsden","year":"2008","unstructured":"Ramsden CM, Kinsella GJ, Ong B, Storey E. Performance of everyday actions in mild Alzheimer\u2019s disease. Neuropsychology. 2008;22(1):17\u201326.","journal-title":"Neuropsychology"},{"issue":"3","key":"77_CR36","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1037\/0894-4105.13.3.381","volume":"13","author":"D Rohrer","year":"1999","unstructured":"Rohrer D, Salmon DP, Wixted JT, Paulsen JS. The disparate effects of Alzheimer\u2019s disease and Huntington\u2019s disease on semantic memory. Neuropsychology. 1999;13(3):381\u20138.","journal-title":"Neuropsychology"},{"issue":"9","key":"77_CR37","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.neuropsychologia.2004.02.001","volume":"42","author":"JD Henry","year":"2004","unstructured":"Henry JD, Crawford JR, Phillips LH. Verbal fluency performance in dementia of the Alzheimer\u2019s type: a meta-analysis. Neuropsychologia. 2004;42(9):1212\u201322.","journal-title":"Neuropsychologia"},{"issue":"4","key":"77_CR38","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/1531-8249(200004)47:4<470::AID-ANA10>3.0.CO;2-M","volume":"47","author":"M Pihlajamaki","year":"2000","unstructured":"Pihlajamaki M, Tanila H, Hanninen T, Kononen M, Laakso M, Partanen K, et al. Verbal fluency activates the left medial temporal lobe: a functional magnetic resonance imaging study. Ann Neurol. 2000;47(4):470\u20136.","journal-title":"Ann Neurol"},{"issue":"3","key":"77_CR39","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1037\/0894-4105.14.3.353","volume":"14","author":"ML Gourovitch","year":"2000","unstructured":"Gourovitch ML, Kirkby BS, Goldberg TE, Weinberger DR, Gold JM, Esposito G, et al. A comparison of rCBF patterns during letter and semantic fluency. Neuropsychology. 2000;14(3):353\u201360.","journal-title":"Neuropsychology"},{"issue":"3\u20134","key":"77_CR40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1155\/2010\/319128","volume":"22","author":"ME Cottingham","year":"2010","unstructured":"Cottingham ME, Hawkins KA. Verbal fluency deficits co-occur with memory deficits in geriatric patients at risk for dementia: Implications for the concept of mild cognitive impairment. Behav Neurol. 2010;22(3\u20134):73\u20139.","journal-title":"Behav Neurol"},{"issue":"3","key":"77_CR41","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/gps.1752","volume":"22","author":"RW Jones","year":"2007","unstructured":"Jones RW, Bayer A, Inglis F, Barker A, Phul R. Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer\u2019s disease. Int J Geriatr Psychiatry. 2007;22(3):258\u201362.","journal-title":"Int J Geriatr Psychiatry"},{"issue":"1","key":"77_CR42","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1001\/archneur.57.1.94","volume":"57","author":"SM Greenberg","year":"2000","unstructured":"Greenberg SM, Tennis MK, Brown LB, Gomez-Isla T, Hayden DL, Schoenfeld DA, et al. Donepezil therapy in clinical practice: a randomized crossover study. Arch Neurol. 2000;57(1):94\u20139.","journal-title":"Arch Neurol"},{"issue":"8","key":"77_CR43","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/S0006-3223(02)01867-X","volume":"53","author":"CH Mallinckrodt","year":"2003","unstructured":"Mallinckrodt CH, Sanger TM, Dube S, DeBrota DJ, Molenberghs G, Carroll RJ, et al. Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biol Psychiatry. 2003;53(8):754\u201360.","journal-title":"Biol Psychiatry"}],"container-title":["CNS Drugs"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40263-013-0077-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-013-0077-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40263-013-0077-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,14]],"date-time":"2019-07-14T07:57:38Z","timestamp":1563091058000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40263-013-0077-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["77"],"URL":"https:\/\/doi.org\/10.1007\/s40263-013-0077-7","relation":{},"ISSN":["1172-7047","1179-1934"],"issn-type":[{"value":"1172-7047","type":"print"},{"value":"1179-1934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6]]}}}