Abstract
Objectives
Mild cognitive impairment (MCI) is etiologically heterogeneous, and a substantial proportion of MCI subjects will develop different dementia disorders. One subtype of this syndrome, amnestic MCI, occurs preferentially but not exclusively in prodromal AD and is characterized by defined deficits of episodic memory.
Design, setting and participants
For a 2-year, double-blinded, placebo-controlled study MCI patients, presenting with an amnestic syndrome but not necessarily based on presumed prodromal AD were randomized.
Intervention
Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or (b) 16 mg galantamine alone or (c) placebo.
Measurements
The primary objective was to explore the differential impact of these interventions on the progression to dementia and on cognitive changes as measured by the ADAScog.
Results
After recruitment of 232 subjects, the trial was halted before reaching the planned sample size, because safety concerns arose in other studies with galantamine in MCI. This resulted in a variable treatment duration of 2–52 weeks. The statistical analysis plan was amended for studying cognitive effects of discontinuing the study medication, which was done separately for galantamine and memantine, and under double-blind conditions. There was one death, no unexpected severe adverse events, and no differences of severe adverse events between the treatment arms. The cognitive changes on the ADAScog were not different among the groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a significant improvement of ADAScog score over placebo before the discontinuation of medication was observed, while amnestic MCI presumably due to other etiologies showed no cognitive changes with broad variation. Cognitive improvement was numerically larger in the combination treatment group than under galantamine alone. Patients who received placebo declined as expected. Discontinuation of galantamine, either as part of the combination regimen or as mono treatment, resulted in a transient decline of the ADAScog score in amnestic MCI of presumed AD etiology, while discontinuation of Memantine did not change the cognitive status.
Conclusion
In an interrupted trial with amnestic MCI subjects the combination of galantamine plus memantine were generally well tolerated. In the subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a short-term combination treatment of galantamine plus memantine was observed, and cognitive decline occurred after discontinuation of galantamine.
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References
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B. Current concepts in mild cognitive impairment. Arch Neurol. 2001 Dec;58(12):1985–1992.
Petersen RC, Parisi JE, Dickson DW, Johnson KA, Knopman DS, Boeve BF, Jicha GA, Ivnik RJ, Smith GE, Tangalos EG, Braak H, Kokmen E. Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol. 2006 May;63(5):665–672.
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL, de Leon M, Feldman H, Ganguli M, Hampel H, Scheltens P, Tiemey MC, Whitehouse P, Winblad B; International Psychogeriatric Association Expert Conference on mild cognitive impairment. Mild cognitive impairment. Lancet. 2006 Apr 15;367(9518):1262–1270.
Tabert MH, Manly JJ, Liu X, Pelton GH, Rosenblum S, Jacobs M, Zamora D, Goodkind M, Bell K, Stem Y, Devanand DP. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Arch Gen Psychiatry. 2006 Aug;63(8):916–924.
Schmidtke K, Hermeneit S. High rate of conversion to Alzheimer’s disease in a cohort of amnestic MCI patients. Int Psychogeriatr. 2008 Feb;20(1):96–10S.
Fleisher AS, Sowell BB, Taylor C, Gamst AC, Petersen RC, Thal LI; Alzheimer’s Disease Cooperative Study. Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2007 May 8;68(19):1588–1595
Komhuber J, Schmidtke K, Frolich L, Pemeczky R, Wolf S, Hampe] H, Jessen F, Heuser I, Peters O, Weih M, Jahn H, Luckhaus C, Hüll M, Gertz HJ, Schröder J, Pantel J, Rienhoff O, Seuchter SA, Rüther E, Henn F, Maier W, Wiltfang J. Early and differential diagnosis of dementia and mild cognitive impairment: design and cohort baseline characteristics of the German Dementia Competence Network. Dement Geriatr Cogn Disord. 2009;27(5):404–417.
Raschetti R, Albanese E, Vanacore N, Maggini M. Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med. 2007 Nov 27;4(11):e338. Review.
Salloway S, Ferris S, Kluger A, Goldman R, Griesing T, Kumar D, Richardson S; Donepezil 401 Study Group. Efficacy of donepezil in mild cognitive impairment: a randomized placebo-controlled trial. Neurology. 2004 Aug 24;63(4):651–657.
Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, Inzitari D, Orgogozo JM, Sauer H, Scheltens P, Scarpini E, Herrmann N, Farlow M, Potkin S, Charles HC, Fox NC, Lane R. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007 Jun;6(6):501–512. Erratum in: Lancet Neurol. 2007 Oct;6(10):849.
Winblad B, Gauthier S, Scinto L, Feldman H, Wilcock GK, Truyen L, Mayorga AJ, Wang D, Brashear HR, Nye JS; GAL-INT-11/18 Study Group. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology. 2008 May 27;70(22):2024–2035.
Komhuber J, Bormann J, Retz W, Hübers M, Riederer P. Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex. Eur J Pharmacol 166 (1989) 589–590
Levin OS, Yunishchenko NA, Dudarova MA. Efficacy of akatinol memantine in moderate cognitive impairments. Neurosci Behav Physiol. 2010 Oct;40(8):926–933.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):317–324.
Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT; Memantine MEM-MD-12 Study Group. Memantine treatment in patients with mild to moderate Alzheimer’s disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Curr Alzheimer Res. 2008 Feb;5(1):83–89.
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Peters, O., Lorenz, D., Fesche, A. et al. A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI. J Nutr Health Aging 16, 544–548 (2012). https://doi.org/10.1007/s12603-012-0062-8
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DOI: https://doi.org/10.1007/s12603-012-0062-8