Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

References

• World Health Organization. World report on ageing and health. Geneva: World Health Organization; 2015. Available from http://www.who.int/ageing/events/world-report-2015-launch. Accessed November 22, 2020.
   Google Scholar
• Wilson T. An introduction to population projections for Australia.Australian Population Studies.2019;3(1):40–56.
   Google Scholar
• Prince MJ, Wimo A, Guerchet MM, Ali GC, Wu Y-T, Prina M. World Alzheimer Report 2015; The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. London: Alzheimer's Disease International, 2015. Available from: http://www.alz.co.uk/research/world-report-2015. Accessed November 22, 2020.
   Google Scholar
• Ahmadi-Abhari S, Guzman-Castillo M, Bandosz P, et al. Temporal trend in dementia incidence since 2002 and projections for prevalence in England and Wales to 2040: modelling study. BMJ. 2017;358:j2856. doi:10.1136/bmj.j2856
   PubMed Web of Science ®Google Scholar
• World Health Organization. Dementia. Geneva: World Health Organization; 2019. Available from: http://www.who.int/news-room/fact-sheets/detail/dementia. Accessed November 21, 2020.
   Google Scholar
• Alzheimer’s Disease International. Dementia Statistics. London: Alzheimer’s Disease International; 2017. Available from: https://www.alz.co.uk/research/statistics. Accessed November 21, 2020.
   Google Scholar
• ICD-10. Organic, including symptomatic, mental disorders (F00-F09); 2016. Available from: https://icd.who.int/browse10/2016/en#/F00-F09. Accessed November 24, 2020..
   Google Scholar
• Dementia Australia 2018a. Types of Dementia. Australia: Dementia Australia; 2018. Available from: https://www.dementia.org.au/information/about-dementia/types-of-dementia. Accessed December 2, 2020.
   Google Scholar
• Dementia Australia 2018c. Alzheimer’s disease. Australia: Dementia Australia; 2018. Available from: https://www.dementia.org.au/about-dementia/types-of-dementia/alzheimer-disease. Accessed December 2, 2020.
   Google Scholar
• Alzheimer’s Association. 2016 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2016;12(4):459–509.
   PubMedGoogle Scholar
• Epperly T, Dunay MA, Boice JL. Alzheimer Disease: pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms. Am Fam Physician. 2017;95(12):771–778.
   PubMed Web of Science ®Google Scholar
• Australian Institute of Health and Welfare 2012. Dementia in Australia. Cat. no. AGE 70. Canberra: AIHW; 2012. Available from: https://www.aihw.gov.au/getmedia/13995.pdf.aspx. Accessed November 25, 2020.
   Google Scholar
• Australian Bureau of Statistics 2019. Causes of Death, Australia, 2019, Catalogue No. 3303.0, ABS. Canberra: Australian Bureau of Statistics (ABS); 2019. Available from: http://www.abs.gov.au/ausstats/[email protected]/mf/3303.0. Accessed December 2, 2020.
   Google Scholar
• Winblad B, Amouyel P, Andrieu S, et al. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15(5):455–532.
   PubMed Web of Science ®Google Scholar
• Malone DC, McLaughlin TP, Wahl PM, et al. Burden of Alzheimer’s disease and association with negative health outcomes. Am J Manag Care. 2009;15(8):481–488.
   PubMed Web of Science ®Google Scholar
• Sharma S, Mueller C, Stewart R, et al. Predictors of falls and fractures leading to hospitalization in people with dementia: a representative cohort study. J Am Med Dir Assoc. 2018;19(7):607–612. doi:10.1016/j.jamda.2018.03.009
   PubMed Web of Science ®Google Scholar
• The National Centre for Social and Economic Modelling NATSEM (2016) Economic Cost of Dementia in Australia 2016–2056; 2017 Feb. Available from: http://www.dementia.org.au/files/NATIONAL/documents/The-economic-cost-of-dementia-in-Australia-2016-to-2056.pdf. Accessed November 12, 2020.
   Google Scholar
• Dyer SM, Harrison SL, Laver K, et al. An overview of systematic reviews of pharmacological and non‐pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia. Int Psychogeriatr. 2017;30(03):1‐15.
   PubMed Web of Science ®Google Scholar
• Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;1:CD005593.
   PubMed Web of Science ®Google Scholar
• O’Brien JT, Holmes C, Jones M, et al. Clinical practice with anti-dementia drugs: a revised (third) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2017;31(2):147–168. doi:10.1177/0269881116680924
   PubMed Web of Science ®Google Scholar
• Rabins PV, Rummans T, Schneider LS, et al. Practice Guideline for the Treatment of Patients with Alzheimer’s Disease and Other Dementias. 2nd ed. USA: American Psychiatric Association; 2014. doi:10.1176/appi.books.9780890423967.152139
   Google Scholar
• Australian Institute of Health and Welfare 2019. Dispensing patterns for anti-dementia medications 2016–17. Cat. no. AGE 95. Canberra: AIHW; 2019. Available from: https://www.aihw.gov.au/reports/dementia/dispensing-patterns-for-anti-dementia-medications/contents. Accessed November 20, 2020.
   Google Scholar
• Calvó-Perxas L, Turró-Garriga O, Vilalta-Franch J, et al. Trends in the Prescription and Long-Term Utilization of Antidementia Drugs Among Patients with Alzheimer’s Disease in Spain: a Cohort Study Using the Registry of Dementias of Girona. Drugs Aging. 2017;34(4):303–310. doi:10.1007/s40266-017-0446-x
   PubMed Web of Science ®Google Scholar
• Moraes FS, Souza MLC, Lucchetti G, Lucchetti ALG. Trends and disparities in the use of cholinesterase inhibitors to treat Alzheimer’s disease dispensed by the Brazilian public health system - 2008 to 2014: a nation-wide analysis. Arq Neuropsiquiatr. 2018;76(7):444–451. doi:10.1590/0004-282x20180064
   PubMed Web of Science ®Google Scholar
• Pariente A, Helmer C, Merliere Y, Moore N, Fourrier-Réglat A, Dartigues JF. Prevalence of cholinesterase inhibitors in subjects with dementia in Europe. Pharmacoepidemiol Drug Saf. 2008;17(7):655–660. doi:10.1002/pds.1613
   PubMed Web of Science ®Google Scholar
• Clague F, Mercer SW, McLean G, Reynish E, Guthrie B. Comorbidity and polypharmacy in people with dementia: insights from a large, population-based cross-sectional analysis of primary care data. Age Ageing. 2017;46(1):33–39.
   PubMed Web of Science ®Google Scholar
• Parsons C. Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem. Ther Adv Drug Saf. 2017;8(1):31–46. doi:10.1177/2042098616670798
   PubMed Web of Science ®Google Scholar
• Hoffmann F, van den Bussche H, Wiese B, et al. Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia. BMC Psychiatry. 2011;11:190. doi:10.1186/1471-244X-11-190
   PubMed Web of Science ®Google Scholar
• Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015;350(mar02 7):h369. doi:10.1136/bmj.h369
   PubMed Web of Science ®Google Scholar
• Masopust J, Protopopová D, Vališ M, et al. Treatment of behavioral and psychological symptoms of dementias with psychopharmaceuticals: a review. Neuropsychiatr Dis Treat. 2018;14:1211–1220. doi:10.2147/NDT.S163842
   PubMed Web of Science ®Google Scholar
• Gabryelewicz T. Pharmacological treatment of behavioral symptoms in dementia patients. Przegl Lek. 2014;71(4):215–220.
   PubMedGoogle Scholar
• Andersen F, Viitanen M, Halvorsen DS, Straume B, Engstad TA. Co-morbidity and drug treatment in Alzheimer’s disease. A cross sectional study of participants in the dementia study in northern Norway. BMC Geriatr. 2011;11:58. doi:10.1186/1471-2318-11-58
   PubMed Web of Science ®Google Scholar
• Fereshtehnejad SM, Johnell K, Eriksdotter M. Anti-dementia drugs and co-medication among patients with Alzheimer’s disease: investigating real-world drug use in clinical practice using the Swedish Dementia Quality Registry (SveDem). Drugs Aging. 2014;31(3):215–224. doi:10.1007/s40266-014-0154-8
   PubMed Web of Science ®Google Scholar
• Crugel M, Paton G, Singh P, et al. Antipsychotics in people with dementia: frequency of use and rationale for prescribing in a UK mental health service. Psychiatrist. 2012;36(5):165–169. doi:10.1192/pb.bp.111.034579
   Google Scholar
• Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;2:CD008191.
   Google Scholar
• Kable A, Fullerton A, Fraser S, et al. Comparison of potentially inappropriate medications for people with dementia at admission and discharge during an unplanned admission to hospital: results from the SMS dementia study. Healthcare (Basel). 2019;7(1):8. doi:10.3390/healthcare7010008
   PubMedGoogle Scholar
• Molist-Brunet N, Sevilla-Sa´nchez D, Ambla´s-Novellas J, et al. Optimizing drug therapy in patients with advanced dementia: a patient-centered approach. Eur Geriatr Med. 2014;5(1):66–71. doi:10.1016/j.eurger.2013.10.011
   Web of Science ®Google Scholar
• von Renteln-kruse W, Neumann L, Klugmann B, et al. Geriatric patients with cognitive impairment: patient characteristics and treatment results on a specialized ward. Dtsch Arztebl Int. 2015;112(7):103–112.
   PubMed Web of Science ®Google Scholar
• Maher RL Jr, Hanlon JT, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57–65. doi:10.1517/14740338.2013.827660
   PubMed Web of Science ®Google Scholar
• Rodrigues MC, Oliveira C. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review. Rev Lat Am Enfermagem. 2016;24:e2800. doi:10.1590/1518-8345.1316.2800
   PubMed Web of Science ®Google Scholar
• Wastesson JW, Morin L, Tan ECK, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opin Drug Saf. 2018;17(12):1185–1196. doi:10.1080/14740338.2018.1546841
   PubMed Web of Science ®Google Scholar
• Reeve E, Trenaman SC, Rockwood K, Hilmer SN. Pharmacokinetic and pharmacodynamic alterations in older people with dementia. Expert Opin Drug Metab Toxicol. 2017;13(6):651–668. doi:10.1080/17425255.2017.1325873
   PubMed Web of Science ®Google Scholar
• Mehta DC, Short JL, Hilmer SN, Nicolazzo JA. Drug access to the central nervous system in Alzheimer’s disease: preclinical and clinical insights. Pharm Res. 2015;32(3):819–839.
   PubMed Web of Science ®Google Scholar
• Massoud L, Agha HA, Taleb M. Pharmacokinetic and pharmacodynamic changes in elderly people. World j Pharm Med. 2017;3(11):14–23.
   Google Scholar
• Hutchison LC, O’Brien CE. Changes in pharmacokinetics and pharmacodynamics in the elderly patient. J Pharm Prac. 2007;20:4–12. doi:10.1177/0897190007304657
   Google Scholar
• Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14. doi:10.1046/j.1365-2125.2003.02007.x
   PubMed Web of Science ®Google Scholar
• Wooten JM. Pharmacotherapy considerations in elderly adults. South Med J. 2012;105(8):437–445. doi:10.1097/SMJ.0b013e31825fed90
   PubMed Web of Science ®Google Scholar
• Kröger E, Mouls M, Wilchesky M, et al. Adverse Drug Reactions Reported with Cholinesterase Inhibitors: an Analysis of 16 Years of Individual Case Safety Reports from VigiBase. Ann Pharmacother. 2015;49(11):1197–1206. doi:10.1177/1060028015602274
   PubMed Web of Science ®Google Scholar
• Pariente A, Sanctussy DJ, Miremont-Salamé G, et al. Factors associated with serious adverse reactions to cholinesterase inhibitors: a study of spontaneous reporting. CNS Drugs. 2010;24(1):55–63. doi:10.2165/11530300-000000000-00000
   PubMed Web of Science ®Google Scholar
• Ali TB, Schleret TR, Reilly BM, Chen WY, Abagyan R. Adverse Effects of Cholinesterase Inhibitors in Dementia, According to the Pharmacovigilance Databases of the United-States and Canada. PLoS One. 2015;10(12):e0144337.
   PubMed Web of Science ®Google Scholar
• Silva T, Reis J, Teixeira J, Borges F. Alzheimer’s disease, enzyme targets and drug discovery struggles: from natural products to drug prototypes. Ageing Res Rev. 2014;15:116–145.
   PubMed Web of Science ®Google Scholar
• Guillozet AL, Smiley JF, Mash DC, Mesulam MM. Butyrylcholinesterase in the life cycle of amyloid plaques. Ann Neurol. 1997;42(6):909–918. doi:10.1002/ana.410420613
   PubMed Web of Science ®Google Scholar
• Giacobini E. Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer’s disease? Drugs Aging. 2001;18(12):891–898. doi:10.2165/00002512-200118120-00001
   PubMed Web of Science ®Google Scholar
• Weinstock M. Selectivity of cholinesterase inhibition: clinical implications for the treatment of Alzheimer’s disease. CNS Drugs. 1999;12(4):307–323. doi:10.2165/00023210-199912040-00005
   Web of Science ®Google Scholar
• Mesulam MM, Geula C. Butyrylcholinesterase reactivity differentiates the amyloid plaques of aging from those of dementia. Ann Neurol. 1994;36(5):722–727. doi:10.1002/ana.410360506
   PubMed Web of Science ®Google Scholar
• Op Den Velde W, Stam FC. Some cerebral proteins and enzyme systems in Alzheimer’s presenile and senile dementia. J Am Geriatr Soc. 1976;24(1):12–16. doi:10.1111/j.1532-5415.1976.tb03247.x
   PubMed Web of Science ®Google Scholar
• Perry EK, Perry RH, Blessed G, Tomlinson BE. Changes in brain cholinesterases in senile dementia of Alzheimer type. Neuropathol Appl Neurobiol. 1978;4(4):273–277. doi:10.1111/j.1365-2990.1978.tb00545.x
   PubMed Web of Science ®Google Scholar
• Geula C, Darvesh S. Butyrylcholinesterase, cholinergic neurotransmission and the pathology of Alzheimer’s disease. Drugs Today (Barc). 2004;40(8):711–721. doi:10.1358/dot.2004.40.8.850473
   PubMed Web of Science ®Google Scholar
• Arendt T, Bruckner MK, Lange M, Bigl V. Changes in acetylcholinesterase and butyrylcholinesterase in Alzheimer’s disease resemble embryonic development – a study of molecular forms. Neurochem Int. 1992;21(3):381–396. doi:10.1016/0197-0186(92)90189-X
   PubMed Web of Science ®Google Scholar
• Davies P. Neurotransmitter-related enzymes in senile dementia of the Alzheimer type. Brain Res. 1979;171(2):319–327. doi:10.1016/0006-8993(79)90336-6
   PubMed Web of Science ®Google Scholar
• 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(3):373–384. doi:10.1002/ana.410340312
   PubMed Web of Science ®Google Scholar
• Maelicke A. Allosteric modulation of nicotinic receptors as a treatment strategy for Alzheimer’s disease. Dement Geriatr Cogn Disord. 2000;11(Suppl 1):11–18. doi:10.1159/000051227
   PubMed Web of Science ®Google Scholar
• Gauthier S. Cholinergic adverse effects of cholinesterase inhibitors in Alzheimer’s disease: epidemiology and management. Drugs Aging. 2001;18(11):853–862. doi:10.2165/00002512-200118110-00006
   PubMed Web of Science ®Google Scholar
• Thompson S, Lanctôt KL, Herrmann N. The benefits and risks associated with cholinesterase inhibitor therapy in Alzheimer’s disease. Expert Opin Drug Saf. 2004;3(5):425–440.
   PubMedGoogle Scholar
• Patel M, Joshi A, Suthar J, Desai S. Drug utilization pattern in patients with different types of dementia in Western India. Int J Alzheimers Dis. 2014;2014:435202.
   PubMedGoogle Scholar
• Li Q, He S, Chen Y, et al. Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer’s disease. Eur J Med Chem. 2018;158:463–477. doi:10.1016/j.ejmech.2018.09.031
   PubMed Web of Science ®Google Scholar
• Cheewakriengkrai L, Gauthier S. A 10-year perspective on donepezil. Expert Opin Pharmacother. 2013;14(3):331–338. doi:10.1517/14656566.2013.760543
   PubMed Web of Science ®Google Scholar
• FDA approved drug products. Available from: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed 19 November 2020.
   Google Scholar
• Howard R, McShane R, Lindesay J, et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med. 2012;366(10):893–903. doi:10.1056/NEJMoa1106668
   PubMed Web of Science ®Google Scholar
• Rodda J, Carter J. Cholinesterase inhibitors and memantine for symptomatic treatment of dementia. BMJ. 2012;344:e2986. doi:10.1136/bmj.e2986
   PubMed Web of Science ®Google Scholar
• Birks JS, Grimley EJ. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2015;4:CD001191.
   Google Scholar
• Tan CC, Yu JT, Wang HF, et al. Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. J Alzheimers Dis. 2014;41(2):615–631. doi:10.3233/JAD-132690
   PubMed Web of Science ®Google Scholar
• Di Santo SG, Prinelli F, Adorni F, et al. A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease. J Alzheimers Dis. 2013;35(2):349–361. doi:10.3233/JAD-122140
   PubMed Web of Science ®Google Scholar
• Tsoi KK, Chan JY, Chan FC, et al. Monotherapy is good enough for patients with mild-to moderate Alzheimer’s disease: a network meta-analysis of 76 randomized controlled trials. Clin Pharmacol Ther. 2019;105(1):121–130. doi:10.1002/cpt.1104
   PubMed Web of Science ®Google Scholar
• Deardorff WJ, Feen E, Grossberg GT. The Use of Cholinesterase Inhibitors Across All Stages of Alzheimer’s Disease. Drugs Aging. 2015;32(7):537–547. doi:10.1007/s40266-015-0273-x
   PubMed Web of Science ®Google Scholar
• Farlow MR, Salloway S, Tariot PN, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24 week, randomized, double-blind study. Clin Ther. 2010;32(7):1234–1251. doi:10.1016/j.clinthera.2010.06.019
   PubMed Web of Science ®Google Scholar
• Sabbagh M, Cummings J, Christensen D, et al. Evaluating the cognitive effects of donepezil 23 mg/ d in moderate and severe Alzheimer’s disease: analysis of effects of baseline features on treatment response. BMC Geriatr. 2013;13:56. doi:10.1186/1471-2318-13-56
   PubMed Web of Science ®Google Scholar
• Molinuevo JL, Frölich L, Grossberg GT, et al. Responder analysis of a randomized comparison of the 13.3 mg/24 h and 9.5 mg/24 h rivastigmine patch. Alzheimers Res Ther. 2015;7(1):9. doi:10.1186/s13195-014-0088-8
   PubMed Web of Science ®Google Scholar
• Farlow MR, Grossberg GT, Sadowsky CH, Meng X, Somogyi MA. 24-week, randomized, controlled trial of rivastigmine patch 13.3 mg/24 h versus 4.6 mg/24 h in severe Alzheimer’s dementia. CNS Neurosci Ther. 2013;19(10):745–752. doi:10.1111/cns.12158
   PubMed Web of Science ®Google Scholar
• Farlow MR, Grossberg G, Gauthier S, Meng X, Olin JT. The ACTION study: methodology of a trial to evaluate safety and efficacy of a higher dose rivastigmine transdermal patch in severe Alzheimer’s disease. Curr Med Res Opin. 2010;26(10):2441–2447. doi:10.1185/03007995.2010.513849
   PubMed Web of Science ®Google Scholar
• Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315–335.
   PubMed Web of Science ®Google Scholar
• Noetzli M, Eap CB. Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer’s disease. Clin Pharmacokinet. 2013;52(4):225–241. doi:10.1007/s40262-013-0038-9
   PubMed Web of Science ®Google Scholar
• Campos C, Rocha NB, Vieira RT, et al. Treatment of Cognitive Deficits in Alzheimer’s disease: a psychopharmacological review. Psychiatr Danub. 2016;28(1):2–12.
   PubMed Web of Science ®Google Scholar
• Cacabelos R. Pharmacogenomics and therapeutic prospects in Alzheimer’s disease. Expert Opin Pharmacother. 2005;6(12):1967–1987. doi:10.1517/14656566.6.12.1967
   PubMed Web of Science ®Google Scholar
• Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol. 2006;9(1):101–124. doi:10.1017/S1461145705005833
   PubMed Web of Science ®Google Scholar
• Heydorn WE. Donepezil (E2020): a new acetylcholinesterase inhibitor. Review of its pharmacology, pharmacokinetics, and utility in the treatment of Alzheimer’s disease. Expert Opin Investig Drugs. 1997;6(10):1527–1535. doi:10.1517/13543784.6.10.1527
   PubMedGoogle Scholar
• Kosasa T, Kuriya Y, Matsui K, Yamanishi Y. Inhibitory effects of donepezil hydrochloride (E2020) on cholinesterase activity in brain and peripheral tissues of young and aged rats. Eur J Pharmacol. 1999;386(1):7–13. doi:10.1016/S0014-2999(99)00741-4
   PubMed Web of Science ®Google Scholar
• Gauthier S. Acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease. Exp Opin Invest Drugs. 1999;8:1511–1520. doi:10.1517/13543784.8.10.1511
   PubMedGoogle Scholar
• Tiseo PJ, Rogers SL, Friedhoff LT. Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration. Br J Clin Pharmacol. 1998;46(Suppl 1):13–18. doi:10.1046/j.1365-2125.1998.0460s1013.x
   PubMed Web of Science ®Google Scholar
• Ohnishi A, Mihara M, Kamakura H, et al. Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer’s disease, in healthy young and elderly subjects. J Clin Pharmacol. 1993;33(11):1086–1091. doi:10.1002/j.1552-4604.1993.tb01945.x
   PubMed Web of Science ®Google Scholar
• Coin A, Pamio MV, Alexopoulos C, et al. Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer’s disease. Eur J Clin Pharmacol. 2016;72(6):711–717. doi:10.1007/s00228-016-2033-1
   PubMed Web of Science ®Google Scholar
• Riyath AA, Ammar BB, Faris TA. In vitro kinetic study of donepezil N-oxide metabolites. Irq J Pharm. 2011;11:1–9.
   Google Scholar
• Winblad B, Engedal K, Soininen H, et al. Donepezil Nordic Study Group. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 2001;57(3):489–495. doi:10.1212/WNL.57.3.489
   PubMed Web of Science ®Google Scholar
• Mohs RC, Doody RS, Morris JC, et al.; “312” Study Group. A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology. 2001;57(3):481–488. doi:10.1212/WNL.57.3.481
   PubMed Web of Science ®Google Scholar
• Rogers SL, Farlow MR, Doody RS, et al.; Donepezil Study Group. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology. 50;1998:136–145. doi:10.1212/WNL.50.1.136
   PubMed Web of Science ®Google Scholar
• Potocnik F. Dementia. S Afr J Psychiatr. 2013;19(3):141–152.
   Web of Science ®Google Scholar
• Jann MW. Rivastigmine, a new generation cholinesterase inhibitor for the treatment of Alzheimer’s disease. Pharmacotherapy. 2000;20(1):1–12. doi:10.1592/phco.20.1.1.34664
   PubMed Web of Science ®Google Scholar
• Hossain M, Jhee SS, Shiovitz T, et al. Estimation of the absolute bioavailability of rivastigmine in patients with mild to moderate dementia of the Alzheimer’s type. Clin Pharmacokinet. 2002;41(3):225–234. doi:10.2165/00003088-200241030-00006
   PubMed Web of Science ®Google Scholar
• Obburu JV, Tammara V, Lesko L, et al. Pharmacokinetic, pharmacodynamic modeling of rivastigmine, a cholinesterase inhibitor, in patients with Alzheimer’s disease. J Clin Pharmacol. 2001;41(10):1082–1090. doi:10.1177/00912700122012689
   PubMed Web of Science ®Google Scholar
• Spencer CM, Noble S. Rivastigmine: a review of its use in Alzheimer’s disease. Drugs Aging. 1998;13(5):391–411. doi:10.2165/00002512-199813050-00005
   PubMed Web of Science ®Google Scholar
• Banks WA. Drug delivery to the brain in Alzheimer’s disease: consideration of the blood-brain barrier. Adv Drug Deliv Rev. 2012;64(7):629–639. doi:10.1016/j.addr.2011.12.005
   PubMed Web of Science ®Google Scholar
• van Assema DM, Lubberink M, Bauer M, et al. Blood-brain barrier P-glycoprotein function in Alzheimer’s disease. Brain. 2012;135(Pt 1):181–189. doi:10.1093/brain/awr298
   PubMed Web of Science ®Google Scholar
• Rösler M, Anand R, Cicin-Sain A, et al. Efficacy and safety of rivastigmine in patients with Alzheimer’s disease: international randomised controlled trial. BMJ. 1999;318(7184):633–638. doi:10.1136/bmj.318.7184.633
   PubMed Web of Science ®Google Scholar
• Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med. 2008;148(5):379–397. doi:10.7326/0003-4819-148-5-200803040-00009
   PubMed Web of Science ®Google Scholar
• Farlow MR. Update on rivastigmine. Neurologist. 2003;9(5):230–234. doi:10.1097/01.nrl.0000087724.73783.5f
   PubMed Web of Science ®Google Scholar
• Isik AT, Bozoglu E, Eker D. aChE and BuChE inhibition by rivastigmin have no effect on peripheral insulin resistance in elderly patients with Alzheimer disease. J Nutr Health Aging. 2012;16(2):139–141. doi:10.1007/s12603-011-0095-4
   PubMed Web of Science ®Google Scholar
• Greenspoon J, Herrmann N, Adam DN. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature. CNS Drugs. 2011;25(7):575–583. doi:10.2165/11592230-000000000-00000
   PubMed Web of Science ®Google Scholar
• Amanatkar HR, Grossberg GT. Transdermal rivastigmine in the treatment of Alzheimer’s disease: current and future directions. Expert Rev Neurother. 2014;14(10):1119–1125. doi:10.1586/14737175.2014.955852
   PubMed Web of Science ®Google Scholar
• Lefevre G, Sedek G, Jhee SS, et al. Pharmacokinetics and pharmacodynamics of the novel Daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer’s disease patients. Clin Pharmacol Ther. 2008;83(1):106–114. doi:10.1038/sj.clpt.6100242
   PubMed Web of Science ®Google Scholar
• Sramek JJ, Frackiewicz EJ, Cutler NR. Review of the acetylcholinesterase inhibitor galantamine. Expert Opin Investig Drugs. 2000;9(10):2393–2402. doi:10.1517/13543784.9.10.2393
   PubMed Web of Science ®Google Scholar
• Bickel U, Thomsen T, Weber W, et al. Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition. Clin Pharmacol Ther. 1991;50(4):420–428. doi:10.1038/clpt.1991.159
   PubMed Web of Science ®Google Scholar
• Bachus R, Bickel U, Thomsen T, Roots I, Kewitz H. The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6. Pharmacogenetics. 1999;9:661–668. doi:10.1097/00008571-199912000-00001
   PubMedGoogle Scholar
• Kewitz H. Pharmacokinetics and metabolism of galanthamine. Drugs Today. 1997;33:265–272. doi:10.1358/dot.1997.33.4.425052
   Web of Science ®Google Scholar
• Raskind MA, Peskind ER, Wessel T, Yuan W; The Galantamine USA-1 Study Group. Galantamine in [Alzheimer’s disease]. A 6-month randomized, placebo-controlled trial with a 6-month extension. Neurology. 2000;54:2261–2268. doi:10.1212/WNL.54.12.2261
   PubMed Web of Science ®Google Scholar
• Zhao Q, Brett M, Van ON, et al. Galantamine pharmacokinetics, safety, and tolerability profiles are similar in healthy Caucasian and Japanese subjects. J Clin Pharmacol. 2002;42(9):1002–1010. doi:10.1177/0091270002042009007
   PubMed Web of Science ®Google Scholar
• Tayeb HO, Yang HD, Price BH, Tarazi FI. Pharmacotherapies for Alzheimer’s disease: beyond cholinesterase inhibitors. Pharmacol Ther. 2012;134(1):8–25.
   PubMed Web of Science ®Google Scholar
• Buckley JS, Salpeter SR. A Risk-Benefit Assessment of Dementia Medications: systematic Review of the Evidence. Drugs Aging. 2015;32(6):453–467. doi:10.1007/s40266-015-0266-9
   PubMed Web of Science ®Google Scholar
• O’Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963–967. doi:10.1001/archneur.65.7.963
   PubMed Web of Science ®Google Scholar
• Doraiswamy PM, Kaiser L, Bieber F, et al. The Alzheimer’s Disease Assessment Scale: evaluation of psychometric properties and patterns of cognitive decline in multicenter clinical trials of mild to moderate Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2001;15(4):174–183. doi:10.1097/00002093-200110000-00003
   PubMed Web of Science ®Google Scholar
• Panisset M, Roudier M, Saxton J, et al. Severe impairment battery. A neuropsychological test for severely demented patients. Arch Neurol. 1994;51(1):41–45. doi:10.1001/archneur.1994.00540130067012
   PubMed Web of Science ®Google Scholar
• Collin C, Wade DT, Davies S, Horne V. The Barthel ADL Index: a reliability study. Int Disabil Stud. 1988;10(2):61–63. doi:10.3109/09638288809164103
   PubMedGoogle Scholar
• Wade DT, Collin C. The Barthel ADL Index: a standard measure of physical disability? Int Disabil Stud. 1988;10(2):64–67. doi:10.3109/09638288809164105
   PubMedGoogle Scholar
• Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–186. doi:10.1093/geront/9.3_Part_1.179
   PubMed Web of Science ®Google Scholar
• Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308–2314. doi:10.1212/WNL.44.12.2308
   PubMed Web of Science ®Google Scholar
• Qaseem A, Snow V, Cross JT, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2008;148(5):370–378. doi:10.7326/0003-4819-148-5-200803040-00008
   PubMed Web of Science ®Google Scholar
• Santaguida PS, Raina P, Booker L, et al. Pharmacological treatment of dementia. Evid Rep Technol Assess (Summ). 2004;97:1–16.
   Google Scholar
• Tricco AC, Ashoor HM, Soobiah C, et al. Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer’s Disease: systematic Review and Network Metaanalysis. J Am Geriatr Soc. 2018;66(1):170–178. doi:10.1111/jgs.15069
   PubMed Web of Science ®Google Scholar
• Trinh NH, Hoblyn J, Mohanty S, et al. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta- analysis. JAMA. 2003;289(2):210–216. doi:10.1001/jama.289.2.210
   PubMed Web of Science ®Google Scholar
• Isik AT, Soysal P, Usarel C. Effects of Acetylcholinesterase Inhibitors on Balance and Gait Functions and Orthostatic Hypotension in Elderly Patients With Alzheimer Disease. Am J Alzheimers Dis Other Demen. 2016;31(7):580–584. doi:10.1177/1533317516666195
   PubMed Web of Science ®Google Scholar
• Winblad B, Kilander L, Eriksson S, et al. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallel-group, placebo-controlled study. Lancet. 2006;367(9516):1057–1065. doi:10.1016/S0140-6736(06)68350-5
   PubMed Web of Science ®Google Scholar
• Froelich L, Andreasen N, Tsolaki M, et al. Long-term treatment of patients with Alzheimer’s disease in primary and secondary care: results from an international survey. Curr Med Res Opin. 2009;25(12):3059–3068. doi:10.1185/03007990903396626
   PubMed Web of Science ®Google Scholar
• Lockhart IA, Mitchell SA, Kelly S. Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer’s disease: systematic review of the “real-world” evidence. Dement Geriatr Cogn Disord. 2009;28:389–403. doi:10.1159/000255578
   PubMed Web of Science ®Google Scholar
• Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging. 2008;3:211–225.
   PubMed Web of Science ®Google Scholar
• Kröger E, Van Marum R, Souverein P, Carmichael PH, Egberts T. Treatment with rivastigmine or galantamine and risk of urinary incontinence: results from a Dutch database study. Pharmacoepidemiol Drug Saf. 2015;24:276–285. doi:10.1002/pds.3741
   PubMed Web of Science ®Google Scholar
• Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11:315–335. doi:10.2174/1570159X11311030006
   PubMed Web of Science ®Google Scholar
• Galligan JJ, Burks TF. Cholinergic neurons mediate intestinal propulsion in the rat. J Pharm Exper Ther. 1986;238(2):594–598.
   PubMed Web of Science ®Google Scholar
• Lewin MJ. Cellular mechanisms and inhibitors of gastric acid secretion. Drugs Today (Barc). 1999;35(10):743–752. doi:10.1358/dot.1999.35.10.561693
   PubMed Web of Science ®Google Scholar
• Full prescription information. Razadyne (galantamine). Available from: https://www.janssenmd.com/pdf/razadyne/PI-Razadyne-RazadyneER.pdf. Assessed November 22, 2020.
   Google Scholar
• Soysal P, Isik AT, Stubbs B, et al. Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87(12):1368–1374. doi:10.1136/jnnp-2016-313660
   PubMed Web of Science ®Google Scholar
• Full prescription information. Aricept (donepezil). Available from: https://www.labeling.pfizer.com/ShowLabeling.aspx?id=510. Accessed November 22, 2020.
   Google Scholar
• Full prescription information. Exelon (rivastigmine). Available from: https://www.pharma.us.novartis.com/product/pi/pdf/exelon.pdf. Accessed November 22, 2020.
   Google Scholar
• Cutler NR, Anand R, Hartman RD, et al. Antiemetic therapy for Alzheimer’s patients receiving the cholinesterase inhibitor SDZ ENA 713 [abstract]. Clin Pharmacol Ther. 1998;63(2):188.
   Web of Science ®Google Scholar
• Kistler PM, Sanders P, Fynn SP, et al. Electrophysiologic and electroanatomic changes in the human atrium associated with age. J Am Coll Cardiol. 2004;44(1):109–116. doi:10.1016/j.jacc.2004.03.044
   PubMed Web of Science ®Google Scholar
• Jones SA, Lancaster MK, Boyett MR. Ageing-related changes of connexins and conduction within the sinoatrial node. J Physiol (Lond). 2004;560(Pt 2):429–437. doi:10.1113/jphysiol.2004.072108
   Google Scholar
• Jane Newby V, Anne Kenny R, McKeith IG. Donepezil and cardiac syncope: case report. Int J Geriatr Psychiatry. 2004;19(11):1110–1112. doi:10.1002/gps.1183
   PubMed Web of Science ®Google Scholar
• Shahani L. Donepezil-associated sick sinus syndrome. J Neuropsychiatry Clin Neurosci. 2014;26(1):E5. doi:10.1176/appi.neuropsych.12110270
   PubMed Web of Science ®Google Scholar
• Park-Wyllie LY, Mamdani MM, Li P, Gill SS, Laupacis A, Juurlink DN. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med. 2009;6(9):e1000157. doi:10.1371/journal.pmed.1000157
   PubMed Web of Science ®Google Scholar
• Tanaka A, Koga S, Hiramatsu Y. Donepezil-induced adverse side effects of cardiac rhythm: 2 cases report of atrioventricular block and Torsade de Pointes. Intern Med. 2009;48(14):1219–1223. doi:10.2169/internalmedicine.48.2181
   PubMed Web of Science ®Google Scholar
• Takaya T, Okamoto M, Yodoi K, et al. Torsades de Pointes with QT prolongation related to donepezil use. J Cardiol. 2009;54(3):507–511. doi:10.1016/j.jjcc.2009.03.011
   PubMed Web of Science ®Google Scholar
• Hadano Y, Ogawa H, Wakeyama T, et al. Donepezil-induced torsades de pointes without QT prolongation. J Cardiol Cases. 2013;8(2):e69–e71. doi:10.1016/j.jccase.2013.05.004
   PubMedGoogle Scholar
• Celik IE, Acar B, Çay S. An unusual cardiovascular adverse effect of donepezil. Intern Med J. 2015;45(8):877–878. doi:10.1111/imj.12827
   PubMed Web of Science ®Google Scholar
• Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med. 2009;169(9):867–873. doi:10.1001/archinternmed.2009.43
   PubMedGoogle Scholar
• Kim DH, Brown RT, Ding EL, Kiel DP, Berry SD. Dementia medications and risk of falls, syncope, and related adverse events meta-analysis of randomized controlled trials. J Am Geriatr Soc. 2011;59(6):1019–1031. doi:10.1111/j.1532-5415.2011.03450.x
   PubMed Web of Science ®Google Scholar
• Hernandez RK, Farwell W, Cantor MD, Lawler EV. Cholinesterase inhibitors and hospitalizations for bradycardia. J Am Geriatr Soc. 2009;57:1997–2003. doi:10.1111/j.1532-5415.2009.02488.x
   PubMed Web of Science ®Google Scholar
• Isik AT, Yildiz GB, Bozoglu E, et al. Cardiac safety of donepezil in elderly patients with Alzheimer disease. Intern Med. 2012;51(6):575–578. doi:10.2169/internalmedicine.51.6671
   PubMed Web of Science ®Google Scholar
• Isik AT, Soysal P, Yay A. Which rivastigmine formula is better for heart in elderly patients with Alzheimer’s disease: oral or patch? Am J Alzheimers Dis Other Demen. 2014;29(8):735–738. doi:10.1177/1533317514536598
   PubMed Web of Science ®Google Scholar
• Isik AT, Bozoglu E, Yay A, et al. Which cholinesterase inhibitor is the safest for the heart elderly patients with Alzheimer’s disease? Am J Alzheimers Dis Other Demen. 2012;27(3):171–174. doi:10.1177/1533317512442999
   PubMed Web of Science ®Google Scholar
• Isik AT, Soysal P, Stubbs B, et al. Cardiovascular Outcomes of Cholinesterase Inhibitors in Individuals with Dementia: a Meta-Analysis and Systematic Review. J Am Geriatr Soc. 2018;66(9):1805–1811. doi:10.1111/jgs.15415
   PubMed Web of Science ®Google Scholar
• Rowland JP, Rigby J, Harper AC, et al. Cardiovascular monitoring with acetylcholinesterase inhibitors: a clinical protocol. Adv Psychiatr Treat. 2007;13:178–184. doi:10.1192/apt.bp.106.002725
   Google Scholar
• Babic T, Zurak N. Convulsions induced by donepezil. J Neurol Neurosurg Psychiatry. 1999;66(3):410. doi:10.1136/jnnp.66.3.410
   PubMed Web of Science ®Google Scholar
• Shareef J, Joseph J, Adithi K. A single case report on hyponatremia seizure induced by acetylcholinesterase inhibitors. Int J Pharm Pharm Sci. 2017;9(7):165–166. doi:10.22159/ijpps.2017v9i7.19057
   Google Scholar
• Ross JS, Shua-Haim JR. Aricept-induced nightmares in Alzheimer’s disease: 2 case reports. J Am Geriatr Soc. 1998;46(1):119–120. doi:10.1111/j.1532-5415.1998.tb01033.x
   PubMed Web of Science ®Google Scholar
• Bouman WP, Pinner G. Violent behavior associated with donepezil. Am J Psychiatry. 1998;155(11):1626–1627. doi:10.1176/ajp.155.11.1626a
   PubMed Web of Science ®Google Scholar
• Yorston GA, Gray R. Hypnopompic hallucinations with donepezil. J Psychopharmacol. 2000;14(3):303–304. doi:10.1177/026988110001400315
   PubMed Web of Science ®Google Scholar
• Wong CW. Pharmacotherapy for Dementia: a Practical Approach to the Use of Cholinesterase Inhibitors and Memantine. Drugs Aging. 2016;33(7):451–460. doi:10.1007/s40266-016-0372-3
   PubMed Web of Science ®Google Scholar
• Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Urinary incontinence: an unrecognised adverse effect with donepezil. Lancet. 2000;356(9229):568. doi:10.1016/S0140-6736(00)02588-5
   PubMed Web of Science ®Google Scholar
• Ale I, Lachapelle JM, Maibach HI. Skin tolerability associated with transdermal drug delivery systems: an overview. Adv Ther. 2009;26(10):920–935. doi:10.1007/s12325-009-0075-9
   PubMed Web of Science ®Google Scholar
• Wohlrab J, Kreft B, Tamke B. Skin tolerability of transdermal patches. Expert Opin Drug Deliv. 2011;8(7):939–948. doi:10.1517/17425247.2011.574689
   PubMed Web of Science ®Google Scholar
• Osada T, Watanabe N, Asano N, Adachi Y, Yamamura K. Adverse drug events affecting medication persistence with rivastigmine patch application. Patient Prefer Adherence. 2018;12:1247–1252. doi:10.2147/PPA.S166680
   PubMed Web of Science ®Google Scholar
• Zannas AS, Okuno Y, Doraiswamy PM. Cholinesterase inhibitors and Pisa syndrome: a pharmacovigilance study. Pharmacotherapy. 2014;34(3):272–278. doi:10.1002/phar.1359
   PubMed Web of Science ®Google Scholar
• Hsu CW, Lee Y, Lee CY, Lin PY. Reversible Pisa Syndrome Induced by Rivastigmine in a Patient With Early-Onset Alzheimer Disease. Clin Neuropharmacol. 2017;40(3):147–148. doi:10.1097/WNF.0000000000000215
   PubMed Web of Science ®Google Scholar
• Miyaoka T, Seno H, Yamamori C, et al. Pisa syndrome due to a cholinesterase inhibitor (donepezil): a case report. J Clin Psychiatry. 2001;62(7):573–574. doi:10.4088/JCP.v62n07d13
   PubMed Web of Science ®Google Scholar
• Fleet JL, McArthur E, Patel A, et al. Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study. CMAJ. 2019;191(37):e1018- e1024. doi:10.1503/cmaj.190337
   PubMed Web of Science ®Google Scholar
• Health Canada. Summary Safety Review - ARICEPT (donepezil) - Risk of Rhabdomyolysis and Neuroleptic Malignant Syndrome [Internet]. Drug Heal Prod. 2015. Available from. http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/aricept-eng.php#fnb1
   Google Scholar
• Ekinci F, Soyaltin UE, Ugur MC, Develi A, Akar H. A rare case of Rhabdomyolysis probably due to donepezil. J Clin Case Rep. 2014;4:465.
   Google Scholar
• Verrico MM, Nace DA, Towers AL. Fulminant chemical hepatitis possibly associated with donepezil and sertraline therapy. J Am Geriatr Soc. 2000;48:1659–1663. doi:10.1111/j.1532-5415.2000.tb03879.x
   PubMed Web of Science ®Google Scholar
• Trenaman SC, Bowles SK, Kirkland S, et al. An examination of three prescribing cascades in a cohort of older adults with dementia. BMC Geriatr. 2021;21(1):297. doi:10.1186/s12877-021-02246-2
   PubMed Web of Science ®Google Scholar
• Vouri SM, Possinger MC, Usmani S, et al. Evaluation of the Potential Acetylcholinesterase Inhibitor-Induced Rhinorrhea Prescribing Cascade. J Am Geriatr Soc. 2020;68(2):440–441. doi:10.1111/jgs.16224
   PubMed Web of Science ®Google Scholar
• Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165(7):808–813. doi:10.1001/archinte.165.7.808
   PubMedGoogle Scholar
• Bowie MW, Slattum PW. Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother. 2007;5:263–303. doi:10.1016/j.amjopharm.2007.10.001
   PubMedGoogle Scholar
• Maher D, Ailabouni N, Mangoni AA, Wiese MD, Reeve E. Alterations in drug disposition in older adults: a focus on geriatric syndromes. Expert Opin Drug Metab Toxicol. 2021;17(1):41–52. doi:10.1080/17425255.2021.1839413
   PubMed Web of Science ®Google Scholar
• Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease - systematic review and meta-analysis. Neurobiol Aging. 2009;30(3):337–352. doi:10.1016/j.neurobiolaging.2007.07.015
   PubMed Web of Science ®Google Scholar
• Nobili A, Garattini S, Mannucci PM. Multiple diseases and polypharmacy in the elderly: challenges for the internist of the third millennium. J Comorbidity. 2011;1:28–44. doi:10.15256/joc.2011.1.4
   PubMedGoogle Scholar
• Onder G, Marengoni A, Russo P, et al. Advanced age and medication prescription: more years, less medications? A Nationwide report from the Italian Medicines Agency. J Am Med Dir Assoc. 2016;17(2):168–172. doi:10.1016/j.jamda.2015.08.009
   PubMed Web of Science ®Google Scholar
• Gustafsson M, Sjölander M, Pfister B, Jonsson J, Schneede J, Lövheim H. Drug-related hospital admissions among old people with dementia. Eur J Clin Pharmacol. 2016;72(9):1143–1153. doi:10.1007/s00228-016-2084-3
   PubMed Web of Science ®Google Scholar
• Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329(7456):15–19. doi:10.1136/bmj.329.7456.15
   PubMed Web of Science ®Google Scholar
• Desai AK, Grossberg GT. Rivastigmine for Alzheimer’s disease. Expert Rev Neurother. 2005;5(5):563–580. doi:10.1586/14737175.5.5.563
   PubMedGoogle Scholar
• Desai AK, Grossberg GT. Review of rivastigmine and its clinical applications in Alzheimer’s disease and related disorders. Expert Opin Pharmacother. 2001;2(4):653–666. doi:10.1517/14656566.2.4.653
   PubMedGoogle Scholar
• Román GC, Rogers SJ. Donepezil: a clinical review of current and emerging indications. Expert Opin Pharmacother. 2004;5(1):161–180. doi:10.1517/14656566.5.1.161
   PubMed Web of Science ®Google Scholar
• Kurz A, Farlow M, Lefèvre G. Pharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer’s disease: a review. Int J Clin Pract. 2009;63(5):799–805. doi:10.1111/j.1742-1241.2009.02052.x
   PubMed Web of Science ®Google Scholar
• Wysokiński A, Sobów T, Kłoszewska I, Kostka T. Mechanisms of the anorexia of aging-a review. Age (Dordr). 2015;37(4):9821. doi:10.1007/s11357-015-9821-x
   PubMed Web of Science ®Google Scholar
• Thompson CM, Johns DO, Sonawane B, et al. Database for physiologically based pharmacokinetic (PBPK) modeling: physiological data for healthy and health-impaired elderly. J Toxicol Environ Health B Crit Rev. 2009;12(1):1–24. doi:10.1080/10937400802545060
   PubMed Web of Science ®Google Scholar
• Hughes VA, Frontera WR, Wood M, et al. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol a Biol Sci Med Sci. 2001;56(5):B209–217. doi:10.1093/gerona/56.5.B209
   PubMed Web of Science ®Google Scholar
• Hubbard RE, O’Mahony MS, Calver BL, Woodhouse KW. Nutrition, inflammation, and leptin levels in aging and frailty. J Am Geriatr Soc. 2008;56(2):279–284. doi:10.1111/j.1532-5415.2007.01548.x
   PubMed Web of Science ®Google Scholar
• Reeve E, Wiese MD, Mangoni AA. Alterations in drug disposition in older adults. Expert Opin Drug Metab Toxicol. 2015;11(4):491–508. doi:10.1517/17425255.2015.1004310
   PubMed Web of Science ®Google Scholar
• Le Couteur DG, Blyth FM, Creasey HM, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol a Biol Sci Med Sci. 2010;65(7):712–717. doi:10.1093/gerona/glq082
   PubMed Web of Science ®Google Scholar
• Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer’s disease. Drugs Aging. 2000;16(3):199–226. doi:10.2165/00002512-200016030-00005
   PubMed Web of Science ®Google Scholar
• Hubbard RE, O’Mahony MS, Calver BL, Woodhouse KW. Plasma esterases and inflammation in ageing and frailty. Eur J Clin Pharmacol. 2008;64(9):895–900. doi:10.1007/s00228-008-0499-1
   PubMed Web of Science ®Google Scholar
• Renton KW. Regulation of drug metabolism and disposition during inflammation and infection. Expert Opin Drug Metab Toxicol. 2005;1(4):629–640. doi:10.1517/17425255.1.4.629
   PubMedGoogle Scholar
• Aitken AE, Richardson TA, Morgan ET. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol. 2006;46:123–149. doi:10.1146/annurev.pharmtox.46.120604.141059
   PubMed Web of Science ®Google Scholar
• Wynne H. Drug metabolism and ageing. J Br Menopause Soc. 2005;11(2):51–56. doi:10.1258/136218005775544589
   PubMedGoogle Scholar
• Zoli M, Magalotti D, Bianchi G, et al. Total and functional hepatic blood flow decrease in parallel with ageing. Age Ageing. 1999;28(1):29–33. doi:10.1093/ageing/28.1.29
   PubMed Web of Science ®Google Scholar
• Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OFW. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology. 1989;9(2):297–301. doi:10.1002/hep.1840090222
   PubMed Web of Science ®Google Scholar
• Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41(2):67–76. doi:10.1080/03602530902722679
   PubMed Web of Science ®Google Scholar
• Butler JM, Begg EJ. Free drug metabolic clearance in elderly people. Clin Pharmacokinet. 2008;47(5):297–321. doi:10.2165/00003088-200847050-00002
   PubMed Web of Science ®Google Scholar
• Tiseo PJ, Vargas R, Perdomo CA, Friedhoff LT. An evaluation of the pharmacokinetics of donepezil HCl in patients with impaired hepatic function. Br J Clin Pharmacol. 1998;46 Suppl 1(Suppl 1):51–55. doi:10.1046/j.1365-2125.1998.0460s1051.x
   PubMedGoogle Scholar
• Tiseo PJ, Foley K, Friedhoff LT. An evaluation of the pharmacokinetics of donepezil HCl in patients with moderately to severely impaired renal function. Br J Clin Pharmacol. 1998;46 Suppl 1(Suppl1):56–60. doi:10.1046/j.1365-2125.1998.0460s1056.x
   PubMedGoogle Scholar
• Fliser D, Zeier M, Nowack R, Ritz E. Renal functional reserve in healthy elderly subjects. J Am Soc Nephrol. 1993;3(7):1371–1377. doi:10.1681/ASN.V371371
   PubMed Web of Science ®Google Scholar
• Viallon A, Guyomarch P, Marjollet O, et al. Creatinine clearance and drug prescriptions for the elderly. A study of 419 patients older than 70 years admitted through the emergency department. Presse Med. 2006;35:413–417. doi:10.1016/S0755-4982(06)74605-X
   PubMed Web of Science ®Google Scholar
• Farlow MR. Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383–1392. doi:10.2165/00003088-200342150-00005
   PubMed Web of Science ®Google Scholar
• Gottwald MD, Rozanski RI. Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer’s disease: review and current status. Expert Opin Investig Drugs. 1999;8(10):1673–1682. doi:10.1517/13543784.8.10.1673
   PubMedGoogle Scholar
• Hrycyna CA. Molecular genetic analysis and biochemical characterization of mammalian P- glycoproteins involved in multidrug resistance. Semin Cell Dev Biol. 2001;12(3):247–256. doi:10.1006/scdb.2000.0250
   PubMed Web of Science ®Google Scholar
• Alavijeh MS, Chishty M, Qaiser MZ, Palmer AM. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx. 2005;2(4):554–571. doi:10.1602/neurorx.2.4.554
   PubMedGoogle Scholar
• van Waterschoot RA, Schinkel AH. A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: recent insights from knockout and transgenic mice. Pharmacol Rev. 2011;63(2):390–410. doi:10.1124/pr.110.002584
   PubMed Web of Science ®Google Scholar
• van Assema DM, Lubberink M, Rizzu P, et al. Blood-brain barrier P-glycoprotein function in healthy subjects and Alzheimer’s disease patients: effect of polymorphisms in the ABCB1 gene. EJNMMI Res. 2012;2(1):57. doi:10.1186/2191-219X-2-57
   PubMed Web of Science ®Google Scholar
• Trifirò G, Spina E. Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems. Curr Drug Metab. 2011;12(7):611–620. doi:10.2174/138920011796504473
   PubMed Web of Science ®Google Scholar
• Bishop JR. Pharmacogenetics. Handb Clin Neurol. 2018;147:59–73.
   PubMedGoogle Scholar
• Noetzli M, Guidi M, Ebbing K, et al. Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance. Br J Clin Pharmacol. 2014;78(1):135–144. doi:10.1111/bcp.12325
   PubMed Web of Science ®Google Scholar
• Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci. 2003;4(2):131–138. doi:10.1038/nrn1035
   PubMed Web of Science ®Google Scholar
• Harold D, Macgregor S, Patterson CE, et al. A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer’s disease. Pharmacogenet Genomics. 2006;16(2):75–77. doi:10.1097/01.fpc.0000189799.88596.04
   PubMed Web of Science ®Google Scholar
• Pola R, Flex A, Ciaburri M, et al. Responsiveness to cholinesterase inhibitors in Alzheimer’s disease: a possible role for the 192 Q/R polymorphism of the PON-1 gene. Neurosci Lett. 2005;382(3):338–341. doi:10.1016/j.neulet.2005.03.027
   PubMed Web of Science ®Google Scholar
• Varsaldi F, Miglio G, Scordo MG, et al. Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer’s disease patients. Eur J Clin Pharmacol. 2006;62(9):721–726. doi:10.1007/s00228-006-0168-1
   PubMed Web of Science ®Google Scholar
• Pilotto A, Franceschi M, D’Onofrio G, et al. Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease. Neurology. 2009;73(10):761–767. doi:10.1212/WNL.0b013e3181b6bbe3
   PubMed Web of Science ®Google Scholar
• Albani D, Martinelli Boneschi F. Replication study to confirm the role of CYP2D6 polymorphism rs1080985 on donepezil efficacy in Alzheimer’s disease patients. J Alzheimers Dis. 2012;30(4):745–749. doi:10.3233/JAD-2012-112123
   PubMed Web of Science ®Google Scholar
• Seripa D, Bizzarro A, Pilotto A, et al. Role of cytochrome P4502D6 functional polymorphisms in the efficacy of donepezil in patients with Alzheimer’s disease. Pharmacogenet Genomics. 2011;21(4):225–230. doi:10.1097/FPC.0b013e32833f984c
   PubMed Web of Science ®Google Scholar
• Campbell NL, Skaar TC, Perkins AJ, et al. Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy. Clin Interv Aging. 2015;10:269–275. doi:10.2147/CIA.S65980
   PubMed Web of Science ®Google Scholar
• Cacabelos R, Martínez R, Fernández-Novoa L, et al. Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics. Int J Alzheimers Dis. 2012;2012:518901.
   PubMedGoogle Scholar
• Liu M, Zhang Y, Huo YR, et al. Influence of the rs1080985 Single Nucleotide Polymorphism of the CYP2D6 Gene and APOE Polymorphism on the Response to Donepezil Treatment in Patients with Alzheimer’s Disease in China. Dement Geriatr Cogn Dis Extra. 2014;4(3):450–456. doi:10.1159/000367596
   PubMedGoogle Scholar
• Choi SH, Kim SY, Na HR, et al. Effect of ApoE genotype on response to donepezil in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 2008;25(5):445–450. doi:10.1159/000124752
   PubMed Web of Science ®Google Scholar
• Cacabelos R. Influence of pharmacogenetic factors on Alzheimer’s disease therapeutics. Neurodegener Dis. 2008;5(3–4):176–178. doi:10.1159/000113695
   PubMed Web of Science ®Google Scholar
• Zanger UM, Raimundo S, Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(1):23–37. doi:10.1007/s00210-003-0832-2
   PubMed Web of Science ®Google Scholar
• Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part I. Clin Pharmacokinet. 2009;48(11):689–723.
   PubMed Web of Science ®Google Scholar
• Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:229–243. doi:10.1517/14622416.3.2.229
   PubMed Web of Science ®Google Scholar
• Martinelli-Boneschi F, Giacalone G, Magnani G, et al. Pharmacogenomics in Alzheimer’s disease: a genome-wide association study of response to cholinesterase inhibitors. Neurobiol Aging. 2013;34(6):1711.e7–13. doi:10.1016/j.neurobiolaging.2012.12.008
   PubMed Web of Science ®Google Scholar
• Lu J, Fu J, Zhong Y, et al. Association between ABCA1 gene polymorphisms and the therapeutic response to donepezil therapy in Han Chinese patients with Alzheimer’s disease. Brain Res Bull. 2018;140:1–4. doi:10.1016/j.brainresbull.2018.03.014
   PubMed Web of Science ®Google Scholar
• Triplitt C. Drug interactions of medications commonly used in diabetes. Diabetes. 2006;19(4):202–211.
   Google Scholar
• Tavassoli N, Sommet A, Lapeyre-Mestre M, Bagheri H, Montrastruc JL. Drug interactions with Cholinesterase inhibitors: an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (Vidal, British National Formulary). Drug Saf. 2007;30(11):1063–1071. doi:10.2165/00002018-200730110-00005
   PubMed Web of Science ®Google Scholar
• Delafuente JC. Understanding and preventing drug interactions in elderly patients. Crit Rev Oncol Hematol. 2003;48(2):133–143. doi:10.1016/j.critrevonc.2003.04.004
   PubMed Web of Science ®Google Scholar
• Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. Drug Saf. 2007;30(10):911–918. doi:10.2165/00002018-200730100-00009
   PubMed Web of Science ®Google Scholar
• Gallicano K, Drusano G. Introduction to drug interactions. In: Piscitelli SC, Rodvold K, editors. Drug Interactions in Infectious Diseases. 2nd ed. Totowa: Humana Press Inc; 2005:1–12.
   Google Scholar
• Pasqualetti G, Tognini S, Calsolaro V, et al. Potential drug-drug interactions in Alzheimer patients with behavioral symptoms. Clin Interv Aging. 2015;10:1457–1466.
   PubMed Web of Science ®Google Scholar
• Magnuson TM, Keller BK, Burke WJ. Extrapyramidal side effects in a patient treated with risperidone plus donepezil. Am J Psychiatry. 1998;155(10):1458–1459. doi:10.1176/ajp.155.10.1458a
   PubMed Web of Science ®Google Scholar
• Mehrpouya M, Ataei S, Nili-Ahmadabadi A. Potential drug interactions with cholinesterase inhibitors in Alzheimer patients: a guideline for Neurologists. J Appl Pharm Sci. 2017;7(1):223–226. doi:10.7324/JAPS.2017.70134
   Google Scholar
• Lin JH, Lu AYH. Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet. 1998;35(5):361–390. doi:10.2165/00003088-199835050-00003
   PubMed Web of Science ®Google Scholar
• McEneny-King A, Edginton AN, Pp R. Investigating the binding interactions of the anti- Alzheimer’s drug donepezil with CYP3A4 and P-glycoprotein. Bioorg Med Chem Lett. 2015;25(2):297–301. doi:10.1016/j.bmcl.2014.11.046
   PubMed Web of Science ®Google Scholar
• Spina E, Scordo MG, D’Arrigo C. Metabolic drug interactions with new psychotropic agents. Fundam Clin Pharmacol. 2003;17(5):517–538. doi:10.1046/j.1472-8206.2003.00193.x
   PubMed Web of Science ®Google Scholar
• Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HCl and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses. Br J Clin Pharmacol. 1998;46(Suppl 1):30–34. doi:10.1046/j.1365-2125.1998.0460s1030.x
   PubMed Web of Science ®Google Scholar
• Defilippi JL, Crismon ML. Drug interactions with cholinesterase inhibitors. Drugs Aging. 2003;20(6):437–444. doi:10.2165/00002512-200320060-00003
   PubMed Web of Science ®Google Scholar
• Carrier L. Donepezil and paroxetine: possible drug interaction. J Am Geriatr Soc. 1999;47(8):1037. doi:10.1111/j.1532-5415.1999.tb01306.x
   PubMed Web of Science ®Google Scholar
• Finch A, Pillans P. P-glycoprotein and its role in drug-drug interactions. Aust Prescr. 2014;37:137–139. doi:10.18773/austprescr.2014.050
   Google Scholar
• US Food and Drug Administration. Clinical drug interaction studies-Cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry; January 2020. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions. Accessed on November 5, 2020.
   Google Scholar
• Takeuchi R, Shinozaki K, Nakanishi T, Tamai I. Local Drug-Drug Interaction of Donepezil with Cilostazol at Breast Cancer Resistance Protein (ABCG2) Increases Drug Accumulation in Heart. Drug Metab Dispos. 2016;44(1):68–74. doi:10.1124/dmd.115.066654
   PubMed Web of Science ®Google Scholar
• Johnell K, Fastbom J. Concurrent use of anticholinergic drugs and cholinesterase inhibitors: register-based study of over 700,000 elderly patients. Drugs Aging. 2008;25:871–877. doi:10.2165/00002512-200825100-00006
   PubMed Web of Science ®Google Scholar
• Modi A, Weiner M, Craig BA, Sands LP, Rosenman MB, Thomas J. Concomitant use of anticholinergics with acetylcholinesterase inhibitors in Medicaid recipients with dementia and residing in nursing homes. J Am Geriatr Soc. 2009;57:1238–1244. doi:10.1111/j.1532-5415.2009.02258.x
   PubMed Web of Science ®Google Scholar
• Walker C, Perks D. Do you know about donepezil and succinylcholine? Anaesthesia. 2002;57:1041. doi:10.1046/j.1365-2044.2002.00117.x
   PubMed Web of Science ®Google Scholar
• Sprung J, Castellani WJ, Srinivasan V, Udayashankar S. The effects of donepezil and neostigmine in a patient with unusual pseudocholinesterase activity. Anesth Analg. 1998;87(5):1203–1205.
   PubMed Web of Science ®Google Scholar
• Sánchez Morillo J, Demartini Ferrari A, Roca de Togores López A. Interacción entre donepezilo y bloqueantes musculares en la enfermedad de Alzheimer [Interaction of donepezil and muscular blockers in Alzheimer’s disease]. Rev Esp Anestesiol Reanim. 2003;50(2):97–100.
   PubMedGoogle Scholar
• Carcenac D, Martin-Hunyadi C, Kiesmann M, Demuynck-Roegel C, Alt M, Kuntzmann F. Syndrome extrapyramidal sous donepezil [Extra-pyramidal syndrome induced by donepezil]. Presse Med. 2000;29(18):992–993.
   PubMed Web of Science ®Google Scholar
• Shimizu S, Mizuguchi Y, Sobue A, Fujiwara M, Morimoto T, Ohno Y. Interaction between anti- Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice. J Pharmacol Sci. 2015;127(4):439–445. doi:10.1016/j.jphs.2015.03.004
   PubMed Web of Science ®Google Scholar
• Bentue-Ferrer D, Tribut O, Polard E, Allain H. Clinically significant drug interactions with cholinesterase inhibitors: a guide for neurologists. CNS Drugs. 2003;17:947–963. doi:10.2165/00023210-200317130-00002
   PubMed Web of Science ®Google Scholar
• [No authors listed]. Bradycardia due to cholinesterase inhibitors: identify adverse effects and take them into account. Prescrire Int. 2011;20(115):95.
   PubMedGoogle Scholar
• Hong YJ, Han HJ, Youn YC, et al. Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer’s disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial. Alzheimers Res Ther. 2019;11(1):37. doi:10.1186/s13195-019-0492-1
   PubMed Web of Science ®Google Scholar
• Christensen DD. Higher-dose (23 mg/day) donepezil formulation for the treatment of patients with moderate-to-severe Alzheimer’s disease. Postgrad Med. 2012;124(6):110–116. doi:10.3810/pgm.2012.11.2589
   PubMed Web of Science ®Google Scholar
• Reyes JF, Vargas R, Kumar D, et al. Steady-state pharmacokinetics, pharmacodynamics and tolerability of donepezil hydrochloride in hepatically impaired patients. Br J Clin Pharmacol. 2004;58(Suppl 1):9–17. doi:10.1111/j.1365-2125.2004.01802.x
   PubMed Web of Science ®Google Scholar
• Ali TB, Schleret TR, Reilly BM, et al. Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United-States and Canada. PLoS One. 2015;10(12):e0144337. doi:10.1371/journal.pone.0144337
   PubMed Web of Science ®Google Scholar
• Sheffrin M, Miao Y, Boscardin WJ, et al. Weight loss associated with cholinesterase inhibitors in individuals with dementia in a national healthcare system. J Am Geriatr Soc. 2015;63(8):1512–1518. doi:10.1111/jgs.13511
   PubMed Web of Science ®Google Scholar
• Vetrano DL, Tosato M, Colloca G, et al. Polypharmacy in nursing home residents with severe cognitive impairment: results from the SHELTER Study. Alzheimers Dement. 2013;9(5):587–593. doi:10.1016/j.jalz.2012.09.009
   PubMed Web of Science ®Google Scholar
• Renn BN, Asghar-Ali AA, Thielke S, et al. A Systematic Review of Practice Guidelines and Recommendations for Discontinuation of Cholinesterase Inhibitors in Dementia. Am J Geriatr Psychiatry. 2018;26(2):134–147. doi:10.1016/j.jagp.2017.09.027
   PubMed Web of Science ®Google Scholar
• Reeve E, Farrell B, Thompson W, et al. Deprescribing cholinesterase inhibitors and memantine In dementia: guideline summary. Med J Aust. 2019;210(4):174–179. doi:10.5694/mja2.50015
   PubMed Web of Science ®Google Scholar
• Corsonello A, Pedone C, Incalzi RA. Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions. Curr Med Chem. 2010;17(6):571–584. doi:10.2174/092986710790416326
   PubMed Web of Science ®Google Scholar
• Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA. 2003;289(9):1107–1116. doi:10.1001/jama.289.9.1107
   PubMed Web of Science ®Google Scholar
• Eshetie TC, Nguyen TA, Gillam MH, Kalisch Ellett LM. A narrative review of problems with medicines use in people with dementia. Expert Opin Drug Saf. 2018;17(8):825–836. doi:10.1080/14740338.2018.1497156
   PubMed Web of Science ®Google Scholar
• Pfister B, Jonsson J, Gustafsson M. Drug-related problems and medication reviews among old people with dementia. BMC Pharmacol Toxicol. 2017;18(1):52. doi:10.1186/s40360-017-0157-2
   PubMed Web of Science ®Google Scholar
• Wucherer D, Thyrian JR, Eichler T, et al. Drug-related problems in community-dwelling primary care patients screened positive for dementia. Int Psychogeriatrics. 2017;29(11):1857–1868. doi:10.1017/S1041610217001442
   PubMed Web of Science ®Google Scholar
• Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. Lancet. 2007;370(9582):185–191. doi:10.1016/S0140-6736(07)61092-7
   PubMed Web of Science ®Google Scholar
• Lau DT, Mercaldo ND, Harris AT, Trittschuh E, Shega J, Weintraub S. Polypharmacy and potentially inappropriate medication use among community-dwelling elders with dementia. Alzheimer Dis Assoc Disord. 2010;24(1):56–63. doi:10.1097/WAD.0b013e31819d6ec9
   PubMed Web of Science ®Google Scholar
• Micromedex® HealthCare Series (internet database) Version 2.0. Greenwood Village, Colorado: Thomson Healthcare Inc; 2013. Available from: http://www.micromedexsolutions.com. Accessed November 22, 2020.
   Google Scholar
• By the 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674–694.
   PubMed Web of Science ®Google Scholar
• Gustafsson M, Sjölander M, Pfister B, Schneede J, Lövheim H. Effects of Pharmacists’ Interventions on Inappropriate Drug Use and Drug-Related Readmissions in People with Dementia-A Secondary Analysis of a Randomized Controlled Trial. Pharmacy (Basel). 2018;6(1):7. doi:10.3390/pharmacy6010007
   PubMedGoogle Scholar
• Heikkilä T, Lekander T, Raunio H. Use of an online surveillance system for screening drug interactions in prescriptions in community pharmacies. Eur J Clin Pharmacol. 2006;62(8):661–665. doi:10.1007/s00228-006-0149-4
   PubMed Web of Science ®Google Scholar
• Horn JR, Hansten PD, Chan LN. Proposal for a new tool to evaluate drug interaction cases. Ann Pharmacother. 2007;41(4):674–680. doi:10.1345/aph.1H423
   PubMed Web of Science ®Google Scholar
• Le Couteur DG, Robinson M, Leverton A, et al. Adherence, persistence and continuation with cholinesterase inhibitors in Alzheimer’s disease. Australas J Ageing. 2012;31(3):164–169. doi:10.1111/j.1741-6612.2011.00564.x
   PubMed Web of Science ®Google Scholar
• Cotrell V, Wild K, Bader T. Medication management and adherence among cognitively impaired older adults. J Gerontol Soc Work. 2006;47(3–4):31–46. doi:10.1300/J083v47n03_03
   PubMedGoogle Scholar
• Thiruchselvam T, Naglie G, Moineddin R, et al. Risk factors for medication nonadherence in older adults with cognitive impairment who live alone. Int J Geriatr Psychiatry. 2012;27(12):1275–1282. doi:10.1002/gps.3778
   PubMed Web of Science ®Google Scholar
• Maxwell CJ, Stock K, Seitz D, Herrmann N. Persistence and adherence with dementia pharmacotherapy: relevance of patient, provider, and system factors. Can J Psychiatry. 2014;59(12):624–631. doi:10.1177/070674371405901203
   PubMed Web of Science ®Google Scholar
• Elliott RA, Goeman D, Beanland C, Koch S. Ability of older people with dementia or cognitive impairment to manage medicine regimens: a narrative review. Curr Clin Pharmacol. 2015;10(3):213–221. doi:10.2174/1574884710666150812141525
   PubMed Web of Science ®Google Scholar
• Arlt S, Lindner R, Rösler A, von Renteln-kruse W. Adherence to medication in patients with dementia: predictors and strategies for improvement. Drugs Aging. 2008;25(12):1033–1047. doi:10.2165/0002512-200825120-00005
   PubMed Web of Science ®Google Scholar
• Kröger E, Tatar O, Vedel I, et al. Improving medication adherence among community-dwelling seniors with cognitive impairment: a systematic review of interventions. Int J Clin Pharm. 2017;39(4):641–656. doi:10.1007/s11096-017-0487-6
   PubMed Web of Science ®Google Scholar