Drug Management of the Dementias

  • Nages Nagaratnam
  • Kujan Nagaratnam
  • Gary Cheuk
Reference work entry

Abstract

Recent increase in our knowledge and understanding of the pathophysiological mechanisms in AD has led to the identification of potential molecular therapeutic targets for the development of specific drugs. To date these new therapeutic approaches are directed on pharmaceutical compounds undergoing randomised controlled trials. The only successful treatment approach to date that has resulted in significant symptomatic benefit has been the cholinesterase inhibition, which prolongs central acetylcholine activity. Two types of cholinesterases are found in the brain – acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). There is evidence that AChE and BuChE have roles in the regulation of ACh levels. The three choline esterase inhibitors are the foremost treatment options for mild to moderate stages of dementia. Randomised clinical trials have shown consistent but modest benefits in all three outcomes. The present review will summarise the min group of cholinesterases with the main focus on their effects and adverse effects.

Keywords

Neurodegenerative diseases Alzheimer’s disease Cholinesterase inhibitors Acetylcholinesterase Butyrylcholinesterase NMDA antagonist 

References

  1. 1.
    Seltzer B, Shewrwin I. A comparison of clinical factors in early and late-onset primary degenerative dementia. One entity or two. Arch Neurol. 1983;40:143–146.CrossRefPubMedGoogle Scholar
  2. 2.
    Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull W, Mayeux R, et al. Effects of age, sex, and ethnicity on association between apolipoprotein E genotype and Alzheimer’s disease: a meta-analysis. JAMA. 1997;278:1349–1356.CrossRefPubMedGoogle Scholar
  3. 3.
    Aprahamiam I, Stella F, Forlenza OV. New treatment strategies for Alzheimer’s disease: is there a hope? Indian J Med Res 2013;138:449–460.Google Scholar
  4. 4.
    Bard F, Fox M, Friedrich S, Seubert D, Kinney GG, et al. Sustained levels of antibodies against Abeta in amyloid –rich regions of the CNS following intravenous dosing in human APP transgenic mice. Exp Neurol. 2012;238:38–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Duyckaerts C, Perruchini C, Lebouvier T, Potier MC. The lesions of Alzheimer’s disease: which therapeutic perspectives? Bull Acad Natl Med. 2008;192(2):303–18.PubMedGoogle Scholar
  6. 6.
    Nicoll JA, Wilkinson D, Holmes C, Steart P, Markhmam H, Weller RO. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med. 2003;9:448–52.CrossRefPubMedGoogle Scholar
  7. 7.
    Bartus RT, Dean RL Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science. 1982;217:408–417.CrossRefPubMedGoogle Scholar
  8. 8.
    Cummings JL, Bach C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Amer J Geriatr Psychiatry. 1998;6 (supp 1) S64–S78.CrossRefGoogle Scholar
  9. 9.
    Francis PT, Palmer AM, Snape M, Willcock GK. The cholinergic hypothesis of Alzheimer’s disease. A review progress. J Neurol Neurosurg Psychiatry. 1999;66:137–147.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Levy R. Is there life in the neurotransmitter approach to the treatment of Alzheimer’s disease ? in Levy R, Howard R, Burns A (eds). Treatment and care in old age Psychiatry. Petersfield, Wrightson Biomedical Publishing Ltd.1993.Google Scholar
  11. 11.
    Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, Delon MC, et al. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science. 1982;215:1237–1239.CrossRefPubMedGoogle Scholar
  12. 12.
    Schneider LS. New therapeutic approaches in Alzheimer’s disease. J Clin Psychiatry. 1996;57:30–36.PubMedGoogle Scholar
  13. 13.
    Kaczmarck LK, Levitan IB. Neuromodulation. The biochemical control of neuronal excitability. Oxford University Press, New York. 1987Google Scholar
  14. 14.
    Maelicke A. Allosteric modulation of nicotinic receptors as a treatment strategy for Alzheimer’s disease. Dement Geriatr Cogn Disord 2000;11:11–18.CrossRefPubMedGoogle Scholar
  15. 15.
    Wright CI, Geula C, Mesulam MM. Neurological cholinesterases in the normal brain and in Alzheimer’s disease: relationship to plaques, tangles and patterns of selective vulnerability. Ann Neurol 1993;34:373–384.CrossRefPubMedGoogle Scholar
  16. 16.
    Grieg NH,Utsuki T,Yu Q-S, Zhu X, Holloway HW, Perry TA, et al. A new therapeutic target in Alzheimer’s disease treatment: attention to butyrylcholinesterase. Curr Med Res Opi. 2001;17:2160–2166.Google Scholar
  17. 17.
    Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978;2:1457–1459.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    MacKnight C. Switching cholinesterase inhibitors: When and how. Geriatr Aging 2007;10(3): 158–161.Google Scholar
  19. 19.
    Winbald B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, et al. A 1-year trial randomized placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57:489–495.CrossRefGoogle Scholar
  20. 20.
    Rogers S, Farlow M, Doody R, Mohs R, Friedhoff LT. On behalf of the Donepezil study group. A 24-week double blind placebo controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 1998;50:136–145.CrossRefPubMedGoogle Scholar
  21. 21.
    Tariot PN, Cummings JL, Katz IR, Mintzer J, Perdomo CA, Schwann EM, et al. A randomized double blind placebo controlled study o the efficacy and safety of donepezil in patients with Alzheimer’s disease in the nursing home setting. J Am Geriatr Soc. 2001 49:1590–1599.CrossRefPubMedGoogle Scholar
  22. 22.
    Corey-Bloom J, Anand R. Veach J, for the ENA 73 B352 Study. A randomized trial evaluating the efficacy and safety of rivastigmine tartrate a new acetylcholinesterase inhibitor in patients with mild to moderately severe Alzheimer’s disease. Int J Geriatr Psychopharmacol 1998;1:55–65.Google Scholar
  23. 23.
    Rosler M, Anand R, Cicin-Sain, Gauthier S, Agid Y, Dal-Bianco P, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease : an international randomized control trial. Br med J 1999;318:633–640.CrossRefGoogle Scholar
  24. 24.
    Cummings JL, Anand R, Koumaras B, Hartman R. Rivastigmine provides behavioral benefits to Ad patients residing in a nursing home: findings from a 26 week trial. Neurology 2000;54:A468.Google Scholar
  25. 25.
    Bullock R, Moulias R, Steinwachs K-C, et al. Effects of rivastigmine on behavioural symptoms in nursing home patients with Alzheimer’s disease: a European, open label multi-centre study. Int Psychogeriatric 2001;13(Suppl 2) Abstract P-248.Google Scholar
  26. 26.
    Olin J, Schneider L. Systematic review of galantamine for Alzheimer’s disease (Cochrane review) In The Cochrane library.1, 2001. Oxford. Update software.Google Scholar
  27. 27.
    Birk J. Cholinesterase inhibitors in Alzheimer’s disease. Cochrane Database Syst. Rev. 2006:CD005593.Google Scholar
  28. 28.
    Hogan DB. The latest in drug therapy for dementia: Gleanings from the third Canadian Consensus Conference on diagnosis and treatment of dementia. Geriatr Aging. 2007; 200710(3):145–151.Google Scholar
  29. 29.
    Rossi ed Australian Medicines Handbook 2008. Adelaide. Australian Medicine Handbook Pty Ltd. 2008.Google Scholar
  30. 30.
    Lundbeck. Australia Ltd. Ebixa products information 26 June 2006.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Nages Nagaratnam
    • 1
  • Kujan Nagaratnam
    • 1
  • Gary Cheuk
    • 2
  1. 1.The University of SydneyWestmead Clinical SchoolWestmeadAustralia
  2. 2.Rehabilitation and Aged Care ServiceBlacktown-Mt Druitt HospitalMount DruittAustralia

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