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The Pharmacological Treatment of Alzheimer's Disease with Cholinesterase Inhibitors and Memantine

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Book cover Pharmacological Mechanisms in Alzheimer's Therapeutics

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The treatment of Alzheimer’s disease (AD) is now a fast evolving field of both basic scientific and clinical research. The use of the currently licensed cholinesterase inhibitor (ChEI) drugs is based on the findings in the midto- late 1970s, and early 1980s, of reduced levels of cholinergic markers in the brain of people who died with AD, mainly in the later stages of severe dementia. These changes were shown to correlate with the severity of pathological and clinical signs of the disease, and led to early attempts to evaluate physostigmine in AD patients (Davis, Mohs, & Tinklenberg, 1979), with more sophisticated trials following later (Asthana et al., 1995; Thal, Ferguson, Mintzer, Raskin, & Targum, 1999).

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References

  • Amar, K., & Wilcock, G. K. (1996). Vascular dementia. British Medical Journals, 312, 227–231.

    CAS  Google Scholar 

  • Asthana, S., Raffaele, K. C., Berardi, A., Greig, N. H., Haxby, J. V., Schapiro, M. B., et al. (1995). Treatment of Alzheimer disease by continuous intravenous infusion of physostigmine. Alzheimer Disease and Associated Disorders, 9, 223–232.

    CAS  PubMed  Google Scholar 

  • Black, S., Roman, G. C., Geldmacher, D. S., Salloway, S., Hecker, J., Burns, A., et al. (2003). Efficacy and tolerability of donepezil in vascular dementia: Positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial. Stroke, 34, 2323–2330.

    Article  CAS  PubMed  Google Scholar 

  • Courtney, C., Farrell, D., Gray, R., Hills, R., Lynch, L., Sellwood, E., et al. (2004). Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): Randomised double-blind trial. Lancet, 363, 2105–2115.

    Article  CAS  PubMed  Google Scholar 

  • Craig, D., & Birks, J. (2005). Rivastigmine for vascular cognitive impairment. Cochrane Database of Systematic Reviews, CD004744.

    Google Scholar 

  • Cummings, J. L., & Masterman, D. L. (1998). Assessment of treatment-associated changes in behavior and cholinergic therapy of neuropsychiatric symptoms in Alzheimer's disease. The Journal of Clinical Psychiatry, 59(Suppl. 13), 23–30.

    PubMed  Google Scholar 

  • Davis, K. L., Mohs, R. C., & Tinklenberg, J. R. (1979). Enhancement of memory by physostigmine. The New England Journal of Medicine, 301, 946.

    CAS  PubMed  Google Scholar 

  • Emre, M., Aarsland, D., Albanese, A., Byrne, E. J., Deuschl, G., De Deyn, P. P., et al. (2004). Rivastigmine for dementia associated with Parkinson's disease. The New England Journal of Medicine, 351, 2509–2518.

    Article  CAS  PubMed  Google Scholar 

  • Erkinjuntti, T., Kurz, A., Gauthier, S., Bullock, R., Lilienfeld, S., & Damaraju, C. V. (2002). Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: A randomised trial. Lancet, 359, 1283–1290.

    Article  PubMed  Google Scholar 

  • Farlow, M., Anand, R., Messina, J., Jr., Hartman, R., & Veach, J. (2000). A 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer's disease. European Neurology, 44, 236–241.

    Article  CAS  PubMed  Google Scholar 

  • Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). Mini-mental state: A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.

    Article  CAS  PubMed  Google Scholar 

  • Francis, P. T., Nordberg, A., & Arnold, S. E. (2005). A preclinical view of cholinesterase inhibitors in neuroprotection: Do they provide more than symptomatic benefits in Alzheimer's disease? Trends in Pharmacological Sciences, 26, 104–111.

    Article  CAS  PubMed  Google Scholar 

  • Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999). The cholinergic hypothesis of Alzheimer's disease: A review of progress. Journal of Neurology, Neurosurgery, and Psychiatry, 66(2), 137–147.

    Article  CAS  PubMed  Google Scholar 

  • Gauthier, S., Wirth, Y., & Mobius, H. J. (2005). Effects of memantine on behavioural symptoms in Alzheimer's disease patients: An analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. International Journal of Geriatric Psychiatry, 20, 459–464.

    Article  CAS  PubMed  Google Scholar 

  • Guy, W. (1976). CGI: Clinical global impressions. In W. Guy (Ed.), ECDEU assessment manual for psychopharmacology (rev. ed., pp. 217–220). Rockville: National Institutes of Health.

    Google Scholar 

  • Hashimoto, M., Kazui, H., Matsumoto, K., Nakano, Y., Yasuda, M., & Mori, E. (2005). Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease? The American Journal of Psychiatry,162, 676–682.

    Article  PubMed  Google Scholar 

  • Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H. P., & van den Bussche H. (2005). Cholinesterase inhibitors for patients with Alzheimer's disease: Systematic review of randomised clinical trials. British Medical Journals,331, 321–327.

    Article  CAS  Google Scholar 

  • Kumar, V., Anand, R., Messina, J., Hartman, R., & Veach, J. (2000). An efficacy and safety analysis of Exelon in Alzheimer's disease patients with concurrent vascular risk factors. European Journal of Neurology,7, 159–169.

    Article  CAS  PubMed  Google Scholar 

  • Levy, M. L., Cummings, J. L., & Kahn-Rose, R. (1999). Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology, 45 (Suppl. 1), 15–22.

    Article  CAS  PubMed  Google Scholar 

  • McKeith, I., Del Ser, T., Spano, P., Emre, M., Wesnes, K., Anand, R., et al. (2000). Efficacy of rivastigmine in dementia with Lewy bodies: A randomised, double-blind, placebo-controlled international study. Lancet,356, 2031–2036.

    Article  CAS  PubMed  Google Scholar 

  • McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., et al. (2005). Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium. Neurology,65, 1863–1872.

    Article  CAS  PubMed  Google Scholar 

  • McShane, R., Areosa, S. A., & Minakaran, N. (2006). Memantine for dementia. Cochrane Database of Systematic Reviews, CD003154.

    Google Scholar 

  • Menendez-Gonzalez, M., Calatayud, M. T., & Blazquez-Menes, B. (2005). Exacerbation of Lewy bodies dementia due to memantine. Journal of Alzheimer's Disease,8, 289–291.

    CAS  PubMed  Google Scholar 

  • Mohs, R. C., & Cohen, L. (1988). Alzheimer's disease assessment scale (ADAS). Psychopharmacology Bulletin,24, 627–650.

    CAS  PubMed  Google Scholar 

  • Nitsch, R. M., Slack, B. E., Wurtman, R. J., & Growdon, J. H. (1992). Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science,258, 304–307.

    Article  CAS  PubMed  Google Scholar 

  • Orgogozo, J. M., Rigaud, A. S., Stoffler, A., Mobius, H. J., & Forette, F. (2002). Efficacy and safety of memantine in patients with mild to moderate vascular dementia: A randomized, placebo-controlled trial (MMM 300). Stroke,33, 1834–1839.

    Article  CAS  PubMed  Google Scholar 

  • Panisset, M., Roudier, M., Saxton, J., & Boller, F. (1994). Severe impairment battery. A neuropsychological test for severely demented patients. Archives of Neurology,51, 41–45.

    CAS  PubMed  Google Scholar 

  • Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., et al. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. The New England Journal of Medicine,352, 2379–2388.

    Article  CAS  PubMed  Google Scholar 

  • Qizilbash, N., Birks, J., Lopez-Arrieta, J., Lewington, S., & Szeto, S. (2000). Tacrine for Alzheimer's disease. [Review] [5 refs]. Cochrane Database of Systematic Reviews, CD000202.

    Google Scholar 

  • Raskind, M. A., Peskind, E. R., Wessel, T., & Yuan, W. (2000). Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology,54, 2261–2268.

    CAS  PubMed  Google Scholar 

  • Reisberg, B., Doody, R., Stoffler, A., Schmitt, F., Ferris, S., & Mobius, H. J. (2003). Memantine in moderate-to-severe Alzheimer's disease. The New England Journal of Medicine,348, 1333–1341.

    Article  CAS  PubMed  Google Scholar 

  • Reisberg, B., Schneider, L., Doody, R., Anand, R., Feldman, H., Haraguchi, H., et al. (1997). Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. Alzheimer Disease and Associated Disorders, 11 (Suppl. 3), 8–18.

    PubMed  Google Scholar 

  • Rogers, S. L., Doody, R. S., Pratt, R. D., & Ieni, J. R. (2000). Long-term efficacy and safety of donepezil in the treatment of Alzheimer's disease: Final analysis of a US multicentre open-label study. European Neuropsychopharmacology,10, 195–203.

    Article  CAS  PubMed  Google Scholar 

  • Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., & Friedhoff, L. T. (1998). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology,50, 136–145.

    CAS  PubMed  Google Scholar 

  • Rogers, S. L., & Friedhoff, L. T. (1996). The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial. The Donepezil Study Group. Dementia,7, 293–303.

    CAS  PubMed  Google Scholar 

  • Rosler, M., Anand, R., Cicin-Sain, A., Gauthier, S., Agid, Y., Dal Bianco, P., et al. (1999). Efficacy and safety of rivastigmine in patients with Alzheimer's disease: International randomised controlled trial. British Medical Journals, 318 (7184), 633–638.

    CAS  Google Scholar 

  • Schmitt, F. A., Ashford, W., Ernesto, C., Saxton, J., Schneider, L. S., Clark, C. M., et al. (1997). The severe impairment battery: Concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Disease and Associated Disorders, 11 (Suppl. 2), S51–S56.

    PubMed  Google Scholar 

  • Sclan, S. G., & Reisberg, B. (1992). Functional assessment staging (FAST) in Alzheimer's disease: Reliability, validity, and ordinality. International Psychogeriatrics, 4 (Suppl. 1), 55–69.

    Article  PubMed  Google Scholar 

  • Summers, W. K., Majovski, L. V., Marsh, G. M., Tachiki, K., & Kling, A. (1986). Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. The New England Journal of Medicine,315, 1241–1245.

    Article  CAS  PubMed  Google Scholar 

  • Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., & Gergel, I. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial. The Journal of American Medical Association,291, 317–324.

    Article  CAS  Google Scholar 

  • Tariot, P. N., Solomon, P. R., Morris, J. C., Kershaw, P., Lilienfeld, S., & Ding, C. (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology,54, 2269–2276.

    CAS  PubMed  Google Scholar 

  • Thal, L. J., Ferguson, J. M., Mintzer, J., Raskin, A., & Targum, S. D. (1999). A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer's disease. Neurology,52, 1146–1152.

    CAS  PubMed  Google Scholar 

  • Trinh, N. H., Hoblyn, J., Mohanty, S., & Yaffe, K. (2003). Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: A meta-analysis. The Journal of American Medical Association,289, 210–216.

    Article  CAS  Google Scholar 

  • Venneri, A., McGeown, W. J., & Shanks, M. F. (2005). Empirical evidence of neuroprotection by dual cholinesterase inhibition in Alzheimer's disease. Neuroreport,16, 107–110.

    Article  CAS  PubMed  Google Scholar 

  • Watkins, P. B., Zimmerman, H. J., Knapp, M. J., Gracon, S. I., & Lewis, K. W. (1994). Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. The Journal of American Medical Association,271, 992–998.

    Article  CAS  Google Scholar 

  • Wilcock, G., Howe, I., Coles, H., Lilienfeld, S., Truyen, L., Zhu, Y., et al. (2003). A long-term comparison of galantamine and donepezil in the treatment of Alzheimer's disease. Drugs Aging,20, 777–789.

    Article  CAS  PubMed  Google Scholar 

  • Wilcock, G. K., Lilienfeld, S., & Gaens, E. (2000). Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: Multicentre randomised controlled trial. Galantamine International-1 Study Group. British Medical Journals,321, 1445–1449.

    Article  CAS  Google Scholar 

  • Wilcock, G., Mobius, H. J., Stoeffler, A., & on behalf of the MMM 500 group (2002). A double-blind placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). International Clinical Psychopharmacology,17, 297–305.

    Article  CAS  PubMed  Google Scholar 

  • Wilcock, G., Stoeffler, A., Sahin, K., & Mobius, H. J. (2000). Neuro-radiological findings and the magnitude of cognitive benefit by memantine treatment. A subgroup analysis of two placebo-controlled clinical trials in vascular dementia. European Neuropsychopharmacology, 10 (Suppl. 3), S360.

    Article  Google Scholar 

  • Wilkinson, D. G., Passmore, A. P., Bullock, R., Hopker, S. W., Smith, R., Potocnik, F. C., et al. (2002). A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease. International Journal of Clinical Practice,56, 441–446.

    CAS  PubMed  Google Scholar 

  • Wimo, A., Wetterholm, A. L., Mastey, V., & Winblad, B. (1998). Evaluation of the healthcare resource utilisation and caregiver time in anti-dementia drug trials. In A. Wimo, B. Jonsson, G. Karlsson, & B. Winblad (Eds.), Health economics of dementia (pp. 465–499). Chichester: John Wiley.

    Google Scholar 

  • Winblad, B., Kilander, L., Eriksson, S., Minthon, L., Batsman, S., Wetterholm, A. L., et al. (2006). Donepezil in patients with severe Alzheimer's disease: Double-blind, parallel-group, placebo-controlled study. Lancet,367, 1057–1065.

    Article  CAS  PubMed  Google Scholar 

  • Winblad, B., & Poritis, N. (1999). Memantine in severe dementia: Results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). International Journal of Geriatric Psychiatry,14, 135–146.

    Article  CAS  PubMed  Google Scholar 

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  1. Nuffield Department of Medicine, University of Oxford, Oxford, UK

    Gordon Keith Wilcock

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Wilcock, G.K. (2007). The Pharmacological Treatment of Alzheimer's Disease with Cholinesterase Inhibitors and Memantine. In: Pharmacological Mechanisms in Alzheimer's Therapeutics. Springer, New York, NY. https://doi.org/10.1007/978-0-387-71522-3_3

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