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Rationalizing Therapeutic Approaches in Alzheimer's Disease

Published online by Cambridge University Press:  07 November 2014

Abstract

Deficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.

Type
Academic Supplement
Copyright
Copyright © Cambridge University Press 2005

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References

REFERENCES

1.Feldman, H, Gracon, S. Alzheimer's disease: symptomatic drugs under development. In: Gauthier, S, ed. Clinical Diagnosis and Management of Alzheimer's Disease. Boston, MA: Butterworth-Heinemann; 1996:239259.Google Scholar
2.Potkin, SG, Anand, R, Hartman, R, Veach, J, Grossberg, G. Impact of Alzheimer's disease and rivastigmine treatment on activities of daily living over the course of mild to moderately severe disease. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:713720.Google Scholar
3.Mohs, RC, Doody, RS, Morris, JC, et al.A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology. 2001;57:481488.CrossRefGoogle ScholarPubMed
4.Tariot, PN, Solomon, PR, Morris, JC, et al; the Galantamine USA-10 Study Group. A 5-month, randomized, placebo-controlled trial of galantamine in AD. Neurology. 2000;54:22692276.Google Scholar
5.Reisberg, B, Doody, R, Stöffler, A, et al.Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003;348:13331341.Google Scholar
6.Data on file. Forest Laboratories, Inc.Google Scholar
7.Winblad, B, Poritis, N. Memantine in severe dementia: results of the M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Geriatr Psychiatry. 1999;14:135146.Google Scholar
8.Tariot, PN, Farlow, MR, Grossberg, GT, et al.Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291:317324.Google Scholar
9.Rogers, SL, Farlow, MR, Doody, RS, Mohs, R, Friedhoff, LT; Donepezil Study Group. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology. 1998;50:136145.Google Scholar
10.Raskind, MA, Peskind, ER, Wessel, T, Yuan, W; the Galantamine USA-1 Study Group. Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. Neurology. 2000;54:22612268.Google Scholar
11.Farlow, M, Anand, R, Messina, J Jr, Hartman, R, Veach, J. A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease. Eur Neurol. 2000;44:236241.Google Scholar
12.Tariot, PN, Cummings, JL, Katz, IR, et al.A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. J Am Geriatr Soc. 2001;49:15901599.Google Scholar
13.Wilkinson, DG, Hock, C, Farlow, M, Van Baelen, B, Schwalen, S. Galantamine provides broad benefits in patients with ‘advanced moderate’ Alzheimer's disease (MMSE < or = 12) for up to six months. Int J Clin Pract. 2002;56:509514.Google Scholar
14.Burns, A, Spiegel, R, Quarg, P. Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease. Int J Geriatr Psychiatry. 2004;19:243249.Google Scholar
15.Peskind, ER, Potkin, SG, Pomara, N, et al. Memantine monotherapy is effective and safe for the treatment of mild to moderate Alzheimer's disease: A randomized controlled trial. Presented at: 8th Congress of the European Federation of Neurological Societies; September 4-7, 2004; Paris, France.Google Scholar
16.Riepe, MW, Adler, G, Ibach, B, et al. Adding memantine to therapy with rivastigmine in patients with mild to moderate Alzheimer's disease: result of a 12-week pilot study. Poster presented at: 17th Annual US Psychiatric and Mental Health Congress; November 18-21, 2004; San Diego, CA.Google Scholar
17.Tariot, PN, Farlow, M, Grossberg, G, et al.Memantine/donepezil dual therapy is superior to placebo/donepezil therapy for treatment of moderate to severe Alzheimer's disease. J Am Geriatr Soc. 2003;51(suppl):S225S226.Google Scholar