Anti-dementia medications – fighting a losing battle?
Abstract
Alzheimer’s disease (AD), the most common cause of dementia, is a growing health, social and economic problem due to the increasing number of sufferers, limited efficacy of available treatment options and high total healthcare costs. It is clinically characterized by cognitive and behavioural impairments, both of which need to be treated appropriately to improve quality of life for patients and their caregivers. Currently available anti-dementia medications provide only modest and transient cognitive benefits. Donepezil, rivastigmine and galantamine (cholinesterase inhibitors) are indicated for the symptomatic treatment of mild to moderately severe AD, while memantine (antagonist of glutamatergic NMDA receptors) is recommended for moderate-to-severe AD. A special focus on behavioral symptoms (e.g. anxiety, depression, aggression) management is required as they cause great suffering in patients/caregivers. The use of medications that can impair cognitive function, such as anticholinergic drugs, should be avoided in patients with dementia. Additionally, interventions that might have the potential to delay or prevent dementia onset in some subjects are focused on minimizing modifiable risk factors (hypertension, diabetes, depression) and maximizing protective factors (higher level of education, physical activity, healthy diet, leisure and social activities). The treatment of AD remains a challenge.
References
Hort J, O'Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, et al; EFNS Scientist Panel on Dementia. EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol. 2010;17(10):1236-48.
Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673-734.
Stefanova, E, rukovodilac; Čovičković Šternić N, urednik. Nacionalni vodič dobre kliničke prakse za dijagnostikovanje i lečenje Alchajmerove bolesti. Republička stručna komisija za izradu i implementaciju vodiča dobre kliničke prakse, Beograd; 2013.
Seeley WW, Miller BL. Alzheimer’s Disease. In: Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 20th ed. New York: McGraw-Hill Education; 2018; p. 3108-15.
Golde TE, DeKosky ST, Galasko D. Alzheimer's disease: The right drug, the right time. Science. 2018;362(6420):1250-1.
Alzheimer's Society - About dementia. [Internet]. [cited 2020 feb 1]. Available from: https://www.alzheimers.org.uk/about-dementia.
Stepanović-Petrović R, Micov A. Farmakoterapija neurodegenerativnih bolesti. U: Ugrešić N, Stepanović-Petrović R, Savić M, urednici. Farmakoterapija za farmaceute. 2. izmenjeno i dopunjeno izdanje. Beograd: Farmaceutski fakultet; 2018. p. 317-51.
Alzheimer's Association. 2019 Alzheimer's disease facts and figures. Alzheimers Dement. 2019;15(3):321-87.
The top 10 causes of death [Internet]. World Health Organization [cited 2020 feb 1]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
Norton S, Matthews FE, Barnes DE, Yaffe K, Brayne C. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-94.
Fink HA, Jutkowitz E, McCarten JR, Hemmy LS, Butler M, Davila H, et al. Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review. Ann Intern Med. 2018;168(1):39-51.
Arab L, Sabbagh MN. Are certain lifestyle habits associated with lower Alzheimer's disease risk? J Alzheimers Dis. 2010;20(3):785-94.
Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, et al. Leisure activities and the risk of dementia in the elderly. N Engl J Med. 2003;348(25):2508-16.
Kivipelto M, Mangialasche F, Ngandu T. Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease. Nat Rev Neurol. 2018;14(11):653-66.
Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401-7.
Rochon PA. Drug prescribing for older adults – UpToDate [Internet]. Wolters Kluwer. [updated 2019 Aug 15; cited 2020 feb 2]. Available from: https://www.uptodate.com/contents/drug-prescribing-for-older-adults.
Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67(2):195-203.
Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol. 2019;15(2):73-88.
National Institute for Health and Care Excellence: Clinical Guidelines. Dementia: Assessment, management and support for people living with dementia and their carers. London: National Institute for Health and Care Excellence (UK); Jun, 2018.
Electronic medicines compendium (emc). [Internet]. [cited 2020 jan 28]. Available from: https://www.medicines.org.uk/emc.
Agencija za lekove i medicinska sredstva. [Internet]. [cited 2020 jan 28]. Available from: https://www.alims.gov.rs/ciril/lekovi/pretrazivanje-humanih-lekova.
Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593.
U.S. Food and Drug dministration. [Internet]. [cited 2020 jan 28]. Available from: https://www.fda.gov/media/86632/download.
Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2018 Jun 18;6:CD001190.
Hogan DB. Long-term efficacy and toxicity of cholinesterase inhibitors in the treatment of Alzheimer disease. Can J Psychiatry. 2014;59(12):618-23.
Jiang S, Li Y, Zhang C, Zhao Y, Bu G, Xu H, et al. M1 muscarinic acetylcholine receptor in Alzheimer's disease. Neurosci Bull. 2014;30(2):295-307.
McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE et al. Memantine for dementia. Cochrane Database Syst Rev. 2019 Mar 20;3:CD003154
Schmidt R, Hofer E, Bouwman FH, Buerger K, Cordonnier C, Fladby T et al. EFNS-ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer's disease. Eur J Neurol. 2015;22(6):889-98.
Tible OP, Riese F, Savaskan E, von Gunten A. Best practice in the management of behavioural and psychological symptoms of dementia. Ther Adv Neurol Disord. 2017;10(8):297-309.
Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer's disease drug development pipeline: 2019. Alzheimers Dement (N Y). 2019;5:272-93.
Egan MF, Kost J, Voss T, Mukai Y, Aisen PS, Cummings JL, et al. Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease. N Engl J Med. 2019;380(15):1408-20.
Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC; AN1792(QS-21)-201 Study Team. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64(9):1553-62.
Schneider L. A resurrection of aducanumab for Alzheimer's disease. Lancet Neurol. 2020;19(2):111-2.
Rickles NM, Skelton JB, Davis J, Hopson J. Cognitive memory screening and referral program in community pharmacies in the United States. Int J Clin Pharm. 2014;36(2):360-7.
Duong S, Patel T, Chang F. Dementia: What pharmacists need to know. Can Pharm J (Ott). 2017;150(2):118-29.
Oswald K. Medicines optimisation in dementia: the role of the community pharmacy. The Pharmaceutical Journal, July 2017, Vol 299, No 7903, online | DOI: 10.1211/PJ.2017.20203134.
