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Chapter 11 - Pharmacological Interventions

from Section 3 - Intervention

Published online by Cambridge University Press:  25 October 2024

Simon Gerhand
Simon Gerhand
Affiliation:
Hywel Dda Health Board, NHS Wales
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Summary

This chapter reviews current options for pharmacological interventions for treating dementia and MCI. For the last 20 years, ACHe inhibitors have been the main option for symptomatic treatment of dementia. The evidence base for their effectiveness is considered. More recent developments are reviewed for pharmacological interventions intended to be disease-modifying. These aim to remove beta amyloid protein, which is the hallmark of Alzheimer’s disease, with the aim of halting the disease’s progress. This is an emerging field, with an evidence base which is still developing, but represents an exciting development.

Keywords

medicationpharmacologicaldrugssymptom-modifyingdisease-modifyingACHe inhibitorsmonoclonal antibodies
Type
Chapter
Information
The Neuropsychology of Dementia
A Clinician's Manual
 , pp. 139 - 147
Publisher: Cambridge University Press
Print publication year: 2024

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References

Buckley, J., & Saltpeter, S. (2015). A risk-benefit assessment of dementia medications: Systematic review of the evidence. Drugs and Ageing, 32 (6), 453–67.CrossRefGoogle ScholarPubMed
Castelli, M. S., McGonigle, P., & Hornby, P. J. (2019). The pharmacology and therapeutic applications of monoclonal antibodies. Pharmacology Research & Perspectives, 7 (6), e00535.CrossRefGoogle ScholarPubMed
Colovic, M. B., Krstic, D. Z., Lazarevic-Pasti, T. D., Bondzic, A. M., & Vasic, V. M. (2013). Acetylcholinesterase inhibitors: Pharmacology and toxicology. Current Neuropharmacology, 11 (3), 315–35.CrossRefGoogle ScholarPubMed
Cummings, J. L., Morstorf, T., & Zhong, K. (2014). Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures. Alzheimer’s Research & Therapy, 6 (4), 1–7.Google ScholarPubMed
Cummings, J. L., & Fox, N. (2017). Defining disease modifying therapy for Alzheimer’s disease. Journal of Prevention of Alzheimer’s Disease, 4 (2), 109–15.Google ScholarPubMed
Fink, H. A., Linskens, E. J., MacDonald, R., et al. (2020). Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia: A systematic review and meta-analysis. Annals of Internal Medicine, 172(10), 656–68.CrossRefGoogle Scholar
Folstein, M., Folsten, S., & McHugh, P. (1975). Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatry Research, 12, 189–98.Google Scholar
Gaspar, R. C., Villarreal, S. A., Bowles, N., et al. (2010). Oligomers of beta-amyloid are sequestered into and seed new plaques in the brains of an AD mouse model. Experimental Neurology, 223 (2), 394–400.CrossRefGoogle ScholarPubMed
Gazzina, S., Manes, M. A., Padovani, A., & Borroni, B. (2017). Clinical and biological phenotypes of frontotemporal dementia: Perspectives for disease modifying therapies. European Journal of Pharmacology, 817, 76–85.CrossRefGoogle ScholarPubMed
Ghezzi, L., Scarpini, E., & Galimberti, D. (2013). Disease-modifying drugs in Alzheimer’s disease. Drug Design, Development and Therapy, 1471–9.Google Scholar
Giacobinni, E. (2001). Selective inhibitors of butyrylcholinesterase: A valid alternative for therapy of Alzheimer’s disease. Drugs and Ageing, 18, 891–8.CrossRefGoogle Scholar
Grossberg, G. T. (2003). Cholinesterase inhibitors for the treatment of Alzheimer’s disease: Getting on and staying on. Current Therapeutic Research, 64 (4), 216–35.CrossRefGoogle Scholar
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I., et al. (2019). Association of amyloid and tau with cognition in preclinical Alzheimer disease: A longitudinal study. JAMA Neurology, 76 (8), 915–24.CrossRefGoogle ScholarPubMed
Holmes, C., Boche, D., Wilkinson, D., et al. (2008). Long-term effects of Aβ42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372 (9634), 216–23.CrossRefGoogle ScholarPubMed
Howard, R., McShane, R., Lindesay, J., et al. (2015). Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease (DOMINO-AD) trial: Secondary and post-hoc analyses. The Lancet Neurology, 14 (12), 1171–1181.CrossRefGoogle ScholarPubMed
Ito, K., Ahadieh, S., Corrigan, B., et al. (2010). Disease progression meta-analysis model in Alzheimer’s disease. Alzheimer’s & Dementia, 6 (1), 39–53.CrossRefGoogle ScholarPubMed
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 Journal, 331 (7512), 321–7.CrossRefGoogle ScholarPubMed
Karlawish, J. H. (2004). Donepezil delay to nursing home placement study is flawed. Journal of the American Geriatric Society, 52, 845CrossRefGoogle Scholar
Knight, R., Khondoker, M., Magill, N., Stewart, R., & Landau, S. (2018). A systematic review and meta-analysis of the effectiveness of acetylcholinesterase inhibitors and memantine in treating the cognitive symptoms of dementia. Dementia and Geriatric Cognitive Disorders, 45(3–4), 131–51.CrossRefGoogle ScholarPubMed
Lalli, G., Schott, J. M., Hardy, J., & De Strooper, B. (2021). Aducanumab: A new phase in therapeutic development for Alzheimer’s disease?. EMBO Molecular Medicine, 13 (8), e14781.CrossRefGoogle ScholarPubMed
Lipton, S. A. (2005). The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: Low-affinity, uncompetitive antagonism. Current Alzheimer Research, 2 (2), 155–65.CrossRefGoogle ScholarPubMed
Liu, K. Y., Schneider, L. S., & Howard, R. (2021) The need to show minimum clinically important differences in Alzheimer’s disease trials. Lancet Psychiatry, 8 (11), 1013–16.CrossRefGoogle ScholarPubMed
Lockwood, P., Ewy, W., Hermann, D., & Holford, N. (2006). Application of clinical trial simulation to compare proof-of-concept study designs for drugs with a slow onset of effect: An example in Alzheimer’s disease. Pharmaceutical Research, 23 (9), 2050–9.CrossRefGoogle ScholarPubMed
Matsunaga, S., Kishi, T., Yasue, I., & Iwata, N. (2016). Cholinesterase inhibitors for Lewy body disorders: A meta-analysis. International Journal of Neuropsychopharmacology, 19 (2), 1–15.CrossRefGoogle Scholar
McHardy, S. F., Wang, H. Y. L., McCowen, S. V., & Valdez, M. C. (2017). Recent advances in acetylcholinesterase inhibitors and reactivators: An update on the patent literature (2012–2015). Expert Opinion on Therapeutic Patents, 27 (4), 455–76.CrossRefGoogle ScholarPubMed
McShane, R., Westby, M. J., & Roberts, E. (2019). Memantine for dementia. Cochrane Database Syst Rev. 2019 Mar 20; 3 (3): CD003154.Google ScholarPubMed
Moreta, M. P. G., Burgos-Alonso, N., Torrecilla, M., Marco-Contelles, J., & Bruzos-Cidón, C. (2021). Efficacy of acetylcholinesterase inhibitors on cognitive function in Alzheimer’s disease. Review of Reviews. Biomedicines, 9 (11), 1689.Google ScholarPubMed
National Institute for Health and Care Excellence (2018). Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease. www.nice.org.uk/guidance/ta217/chapter/1-Guidance.Google Scholar
National Institute for Health and Clinical Excellence (2009). Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease (amended); NICE technology appraisal guidance 111. National Institute for Health and Clinical Excellence: London, UK.Google Scholar
Nordberg, A., Ballard, C., Bullock, R., Darreh-Shori, T., & Somogyi, M. (2013). A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. The Primary Care Companion for CNS Disorders, 15 (2), 26731.CrossRefGoogle ScholarPubMed
O’Brien, J. T., Holmes, C., Jones, M., et al. (2017). Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology. Journal of Psychopharmacology, 31 (2), 147–68.CrossRefGoogle ScholarPubMed
Rédaction, P. (2018). Médicaments de la maladie d’Alzheimer: Enfin non remboursables en France! Revue Prescrire, 38, 1–2.Google Scholar
Rosen, W. G., Mohs, R. C., & Davis, K. L. (1984). A new rating scale for Alzheimer’s disease. The American Journal of Psychiatry, 141, 1356–64. http://dx.doi.org/10.1176/ajp.141.11.1356.Google ScholarPubMed
Schneider, L. S., & Qizilbash, N. (2004). Delay in nursing home placement with donepezil. Journal of the American Geriatric Society, 52, 1024–6.CrossRefGoogle ScholarPubMed
Sims, J. R., Zimmer, J. A., Evans, C. D., et al. (2023). Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA, 330(6), 512–27.CrossRefGoogle ScholarPubMed
Therneau, T. M., Knopman, D. S., Lowe, V. J., et al. (2021). Relationships between β-amyloid and tau in an elderly population: An accelerated failure time model. NeuroImage, 242, 118440.CrossRefGoogle Scholar
Thomas, S., & Grossberg, G. (2009). Memantine: A review of studies into its safety and efficacy in treating Alzheimer’s disease and other dementias. Clinical Interventions in Aging, 4, 367–77.Google ScholarPubMed
Walsh, S., Merrick, R., Milne, R. & Brayne, C. (2021). Aducanumab for Alzheimer’s disease? British Medical Journal, 374, n1682.CrossRefGoogle ScholarPubMed
Wessels, A. M., Siemers, E. R., Yu, P., et al. (2015). A combined measure of cognition and function for clinical trials: The integrated Alzheimer’s Disease Rating Scale (iADRS). The Journal of Prevention of Alzheimer’s disease, 2 (4), 227.Google ScholarPubMed
World Health Organization (2022). Clinical Trials. www.who.int/health-topics/clinical-trials/#tab=tab_1.Google Scholar
Yang, T., Li, S., Xu, H., Walsh, D. M., Selkoe, D. J. (2017). Large soluble oligomers of amyloid-protein from Alzheimer’s brain are far less neuroactive than the smaller oligomers to which they dissociate. Journal of Neuroscience, 37 (1), 152–63.CrossRefGoogle Scholar

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