- Email: [email protected]
Anticholinergic Medications and Cognition
EDITORIALS
Anticholinergic Medications and Cognition John E. Morley, MB, BCh The concept that anticholinergic drugs could have negative effects on cognition was brought to the fore in the 1980s when anticholinergic drugs used to treat parkinsonism were shown to induce delirium1 and drug-induced ‘‘alzheimerism.’’2 These findings were brought full circle by the recent article in the Journal by Lowry et al.3 showing that patients with a high anticholinergic risk score was negatively associated with a number of components of the Barthel Index. This study highlights the risk of functional decline in the frail elderly residing in nursing homes.4–8 Even more concerning is the use of anticholinergic drugs in persons with dementia. A major cause of dementia is a decrease in cholinergic function.9,10 Kolanowski et al.11 reported in their nursing home study that 81.6% of their subjects with dementia were prescribed at least one drug with anticholinergic properties. Olsson et al.12 found that anticholinergic drugs were prescribed to 20.7% of residents in Swedish nursing homes and 18.5% of those in special care units for dementia.12 The 2004 U.S. National Nursing Home Survey data showed that 73.6% of the nursing home population with dementia used anticholinergic drugs, with 21.3% using medications with marked anticholinergic properties.13 In Scotland, institutionalization was highly associated with the use of antimuscarinic drugs.14 Polypharmacy, which is highly prevalent in nursing homes, is a major risk factor for persons to receive anticholinergic drugs.15–18 A community study in persons 50 to 64 years of age showed that anticholinergic medications are associated with a lower level of complex attention.19 A review of 27 studies in which serum anticholinergic activity was measured found that anticholinergic activity had a negative impact on cognitive performance of older adults.20 A large community study in France reported that older persons taking anticholinergic medications were more likely to show cognitive decline (women showed declines in verbal fluency and global cognitive functioning and men showed declines in visual memory and executive function).21 Discontinuing anticholinergic medicines lead to improved cognition. In a Japanese study, psychotropic medications were associated with increased serum anticholinergic activity and worsening cognition.22,23 In an Australian study, a high anticholinergic load in persons over 60 years Division of Geriatric Medicine, Saint Louis University School of Medicine, St Louis, MO. Address correspondence to John E. Morley, MB, BCh, Division of Geriatric Medicine, Saint Louis University, St. Louis, Missouri. E-mail: [email protected]
Copyright Ó2011 American Medical Directors Association DOI:10.1016/j.jamda.2011.07.008 EDITORIALS
of age was associated with a decline in psychomotor speed and executive function.24 In addition, a prospective study found that anticholinergics increased the number of hospital days per person per year but did not increase mortality.25 In African Americans, a 6-year longitudinal study found increased cognitive impairment in those using anticholinergic drugs.26 In persons with Alzheimer’s disease who have the APOE4 allele, there was an increased risk of anticholinergic drugs producing cognitive impairment.27 Behavior abnormalities, including psychoses, are common in Alzheimer’s disease.28–31 There is now evidence that anticholinergic drugs can precipitate psychotic behavior.32 As antipsychotics have multiple other negative effects, it seems that their use should be highly curtailed in nursing homes.33–36 Perhaps most troublesome is the common use of anticholinergic drugs in combination with acetyl cholinesterase inhibitors. In a study of Indiana Medicaid recipients with dementia living in nursing homes, 46.7% were receiving an anticholinergic drug and a cholinesterase inhibitor concomitantly.37 In an Australian study, 32% of persons receiving a cholinesterase inhibitor also took an anticholinergic drug.38 There was a statistically significant increase in the use of anticholinergic drugs after the initiation of cholinesterase inhibitors. Weight loss is common in nursing homes leading to decreased fat and a decline in albumin.39–42 Many anticholinergic drugs are either albumin bound or fat soluble, necessitating a decrease in their dosage when weight loss occurs. Two readily available scales are available to allow clinicians to judge the anticholinergic activity of drugs. The Anticholinergic Risk Scale is available at http://www.kfmc.org/providers/ rx/Anticholinergic%20Risk%20Scale%20Table.pdf. The Anticholinergic Risk Scale divides the drugs into three categories from mild anticholinergic effects/proved with receptor assay to severe effects. While many of these drugs are well known to physicians to have anticholinergic activity, others, such as many of the selective serotonin reuptake inhibitor antidepressants, H2 antagonists, convulsants, and cardiovascular drugs, will be surprising to many. The Anticholinergic Cognitive Burden scale is available at http://www.indydiscoverynetwork.org/. The Anticholinergic Cognitive Burden divides the drugs into two classes: those with possible and those with definite anticholinergic activity. A final take-home message is that when a person needs a definite anticholinergic, it would seem that to decrease side effects cholinesterase inhibitors should not be used. REFERENCES References available at www.jamda.com with your JAMDA login. Morley
543
REFERENCES 1. Agnoli A, Martucci N, Manna V, et al. Effect of cholinergic and anticholinergic drugs on short-term memory in Alzheimer’s dementia: A neuropsychological and computerized electroencephalographic study. Clin Neuropharmacol 1983;6:311–323. 2. Kurlan R, Como P. Drug-induced alzheimerism. Arch Neurol 1988;45: 356–357. 3. Lowry E, Woodman RJ, Soiza RL, et al. Associations between the Anticholinergic Risk Scale score and physical function: Potential implications for adverse outcomes in older hospitalized patients. J Am Med Dir Assoc 2011 [Oct]. 4. Abellan van Kan G, Rolland YM, Morley JE, et al. Frailty: Toward a clinical definition. J Am Med Dir Assoc 2008;9:71–72. 5. Rockwood K, Abeysundera MJ, Mitnitski A. How should we grade frailty in nursing home patients? J Am Med Dir Assoc 2007;8:595–603. 6. Gobbens RJ, van Assen MA, Luijkx KG, et al. Determinants of frailty. J Am Med Dir Assoc 2010;11:356–364. 7. Morley JE. Anabolic steroids and frailty. J Am Med Dir Assoc 2010;11: 533–536. 8. Abellan van Kan G, Rolland Y, Bergman H, et al. The I.A.N.A. Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging 2008;12:29–37. 9. Lee M, Chodosh J. Dementia and life expectancy: What do we know? J Am Med Dir Assoc 2009;10:466–471. 10. Morley JE. Alzheimer’s disease: Future treatments. J Am Med Dir 2011; 12:1–7. 11. Kolanowski A, Fick DM, Campbell J, et al. A preliminary study of anticholinergic burden and relationship to a quality of life indicator, engagement in activities, in nursing home residents with dementia. J Am Med Dir Assoc 2009;10:252–257. 12. Olsson J, Bergman A, Carlsten A, et al. Quality of drug prescribing in elderly people in nursing homes and special care units for dementia: A cross-sectional computerized pharmacy register analysis. Clin Drug Investig 2010;30:289–300. 13. Chatterjee S, Mehta S, Sherer JT, et al. Prevalence and predictors of anticholinergic medication use in elderly nursing home residents with dementia: Analysis of data from the 2004 National Nursing Home Survey. Drugs Aging 2010;27:987–997. 14. Lowry E, Woodman RJ, Soiza RL, et al. Clinical and demographic factors associated with antimuscarinic medication use in older hospitalized patients. Hosp Pract (Minneap) 2011;39:30–36. 15. Fitzgerald SP, Bean NG. An analysis of the interactions between individual comorbidities and their treatments—implications for guidelines and polypharmacy. J Am Med Dir Assoc 2010;11:475–484. 16. Gokce Kutsal Y, Barak A, et al. Polypharmacy in the elderly: A multicenter study. J Am Med Dir Assoc 2009;10:486–490. 17. Morley JE. Polypharmacy in the nursing home. J Am Med Dir Assoc 2009;10:289–291. 18. Miles RW. A conversation: Polypharmacy in the nursing home. J Am Med Dir Assoc 2010;11:296–297. 19. Low LF, Anstey KL, Sachdev P. Use of medications with anticholinergic properties and cognitive function in a young-old community sample. Int J Geriatr Psychiatry 2009;24:578–584. 20. Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: A clinical review. Clin Interv Aging 2009;4:225–233. 21. Carriere I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-City Study. Arch Intern Med 2009;169: 1317–1324.
543.e1 Morley
22. Hori K, Konishi K, Watanabe K, et al. Influence of anticholinergic activity in serum on clinical symptoms of Alzheimer’s disease. Neuropsychobiology 2011;63:147–153. 23. Konishi K, Hori K, Uchida H, et al. Adverse effects of anticholinergic activity on cognitive functions in Alzheimer’s disease. Psychogeriatrics 2010;10:34–38. 24. Sittironnarit G, Ames D, Bush AI, et al. Effects of anticholinergic drugs on cognitive function in older Australians: Results from the AIBL Study. Dement Geriatr Cogni Disord 2011;31:173–178. 25. Uusvaara J, Pitkala KH, Kautiainen H, et al. Association of anticholinergic drugs with hospitalization and mortality among older cardiovascular patients: A prospective study. Drugs Aging 2011;28:131–138. 26. Campbell NL, Boustani MA, Lane KA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology 2010;75:152–159. 27. Uusvaara J, Pitkala KH, Tienari PJ, et al. Association between anticholinergic drugs and apolipoprotein E epsilon4 allele and poorer cognitive function in older cardiovascular patients: a cross-sectional study. J Am Geriatr Soc 2009;57:427–431. 28. Volicer L. Toward better terminology of behavioral symptoms of dementia. J Am Med Dir Assoc 2011. Jan 14 [Epub ahead of print]. 29. Nazir A, Arling G, Perkins AJ, Boustani M. Monitoring quality of care for nursing home Residents with behavioral and psychological symptoms related to dementia. J Am Med Dir Assoc 2010. Dec 29 [Epub ahead of print]. 30. Voyer P, Richard S, McCusker J, et al. Detection of delirium and its symptoms by nurses working in a long-term care facility. J Am Med Dir Assoc 2010. Dec 15 [Epub ahead of print]. 31. Morley JE. Clinical practice in nursing homes as a key for progress. J Nutr Health Aging 2010;14:586–593. 32. Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: A potential risk factor for psychosis onset in Alzheimer’s disease? Exp Opin Drug Saf 2009;8:549–557. 33. Cornege-Blokland E, Kleijer BC, Hertogh CM, et al. Reasons to prescribe antipsychotics for the behavioral symptoms of dementia: A survey in Dutch nursing homes among physicians, nurses, and family caregiver. J Am Med Dir Assoc 2010. Dec 14 [Epub ahead of print]. 34. Lester P, Kohen I, Stefanacci RG, et al. Antipsychotic drug use since the FDA black box warning: Survey of nursing home policies. J Am Med Dir Assoc 2010. Sep 30 [Epub ahead of print]. 35. Jalbert JJ, Eaton CB, Miller SC, et al. Antipsychotic use and the risk of hip fracture among older adults afflicted with dementia. J Am Med Dir Assoc 2010;11:120–127. 36. Cabrera MA, Dellaroza MS, Trelha CS, et al. Psychoactive drugs as risk factors for functional decline among noninstitutionalized dependent elderly people. J Am Med Dir Assoc 2010;11:519–522. 37. Modi A, Weiner M, Craig BA, et al. 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. 38. Robinson M, Rowett D, Leverton A, et al. Changes in utilization of anticholinergic drugs after initiation of cholinesterase inhibitors. Pharmacoepidemiol Drug Saf 2009;18:659–664. 39. Morley JE. Anorexia, weight loss, and frailty. J Am Med Dir Assoc 2010; 11:225–228. 40. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229–230. 41. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637–3647. 42. Morley JE. Assessment of malnutrition in older persons: A focus on the Mini Nutritional Assessment. J Nutr Health Aging 2011;15:87–90.
JAMDA – October 2011
Anticholinergic Medications and Cognition John E. Morley, MB, BCh The concept that anticholinergic drugs could have negative effects on cognition was brought to the fore in the 1980s when anticholinergic drugs used to treat parkinsonism were shown to induce delirium1 and drug-induced ‘‘alzheimerism.’’2 These findings were brought full circle by the recent article in the Journal by Lowry et al.3 showing that patients with a high anticholinergic risk score was negatively associated with a number of components of the Barthel Index. This study highlights the risk of functional decline in the frail elderly residing in nursing homes.4–8 Even more concerning is the use of anticholinergic drugs in persons with dementia. A major cause of dementia is a decrease in cholinergic function.9,10 Kolanowski et al.11 reported in their nursing home study that 81.6% of their subjects with dementia were prescribed at least one drug with anticholinergic properties. Olsson et al.12 found that anticholinergic drugs were prescribed to 20.7% of residents in Swedish nursing homes and 18.5% of those in special care units for dementia.12 The 2004 U.S. National Nursing Home Survey data showed that 73.6% of the nursing home population with dementia used anticholinergic drugs, with 21.3% using medications with marked anticholinergic properties.13 In Scotland, institutionalization was highly associated with the use of antimuscarinic drugs.14 Polypharmacy, which is highly prevalent in nursing homes, is a major risk factor for persons to receive anticholinergic drugs.15–18 A community study in persons 50 to 64 years of age showed that anticholinergic medications are associated with a lower level of complex attention.19 A review of 27 studies in which serum anticholinergic activity was measured found that anticholinergic activity had a negative impact on cognitive performance of older adults.20 A large community study in France reported that older persons taking anticholinergic medications were more likely to show cognitive decline (women showed declines in verbal fluency and global cognitive functioning and men showed declines in visual memory and executive function).21 Discontinuing anticholinergic medicines lead to improved cognition. In a Japanese study, psychotropic medications were associated with increased serum anticholinergic activity and worsening cognition.22,23 In an Australian study, a high anticholinergic load in persons over 60 years Division of Geriatric Medicine, Saint Louis University School of Medicine, St Louis, MO. Address correspondence to John E. Morley, MB, BCh, Division of Geriatric Medicine, Saint Louis University, St. Louis, Missouri. E-mail: [email protected]
Copyright Ó2011 American Medical Directors Association DOI:10.1016/j.jamda.2011.07.008 EDITORIALS
of age was associated with a decline in psychomotor speed and executive function.24 In addition, a prospective study found that anticholinergics increased the number of hospital days per person per year but did not increase mortality.25 In African Americans, a 6-year longitudinal study found increased cognitive impairment in those using anticholinergic drugs.26 In persons with Alzheimer’s disease who have the APOE4 allele, there was an increased risk of anticholinergic drugs producing cognitive impairment.27 Behavior abnormalities, including psychoses, are common in Alzheimer’s disease.28–31 There is now evidence that anticholinergic drugs can precipitate psychotic behavior.32 As antipsychotics have multiple other negative effects, it seems that their use should be highly curtailed in nursing homes.33–36 Perhaps most troublesome is the common use of anticholinergic drugs in combination with acetyl cholinesterase inhibitors. In a study of Indiana Medicaid recipients with dementia living in nursing homes, 46.7% were receiving an anticholinergic drug and a cholinesterase inhibitor concomitantly.37 In an Australian study, 32% of persons receiving a cholinesterase inhibitor also took an anticholinergic drug.38 There was a statistically significant increase in the use of anticholinergic drugs after the initiation of cholinesterase inhibitors. Weight loss is common in nursing homes leading to decreased fat and a decline in albumin.39–42 Many anticholinergic drugs are either albumin bound or fat soluble, necessitating a decrease in their dosage when weight loss occurs. Two readily available scales are available to allow clinicians to judge the anticholinergic activity of drugs. The Anticholinergic Risk Scale is available at http://www.kfmc.org/providers/ rx/Anticholinergic%20Risk%20Scale%20Table.pdf. The Anticholinergic Risk Scale divides the drugs into three categories from mild anticholinergic effects/proved with receptor assay to severe effects. While many of these drugs are well known to physicians to have anticholinergic activity, others, such as many of the selective serotonin reuptake inhibitor antidepressants, H2 antagonists, convulsants, and cardiovascular drugs, will be surprising to many. The Anticholinergic Cognitive Burden scale is available at http://www.indydiscoverynetwork.org/. The Anticholinergic Cognitive Burden divides the drugs into two classes: those with possible and those with definite anticholinergic activity. A final take-home message is that when a person needs a definite anticholinergic, it would seem that to decrease side effects cholinesterase inhibitors should not be used. REFERENCES References available at www.jamda.com with your JAMDA login. Morley
543
REFERENCES 1. Agnoli A, Martucci N, Manna V, et al. Effect of cholinergic and anticholinergic drugs on short-term memory in Alzheimer’s dementia: A neuropsychological and computerized electroencephalographic study. Clin Neuropharmacol 1983;6:311–323. 2. Kurlan R, Como P. Drug-induced alzheimerism. Arch Neurol 1988;45: 356–357. 3. Lowry E, Woodman RJ, Soiza RL, et al. Associations between the Anticholinergic Risk Scale score and physical function: Potential implications for adverse outcomes in older hospitalized patients. J Am Med Dir Assoc 2011 [Oct]. 4. Abellan van Kan G, Rolland YM, Morley JE, et al. Frailty: Toward a clinical definition. J Am Med Dir Assoc 2008;9:71–72. 5. Rockwood K, Abeysundera MJ, Mitnitski A. How should we grade frailty in nursing home patients? J Am Med Dir Assoc 2007;8:595–603. 6. Gobbens RJ, van Assen MA, Luijkx KG, et al. Determinants of frailty. J Am Med Dir Assoc 2010;11:356–364. 7. Morley JE. Anabolic steroids and frailty. J Am Med Dir Assoc 2010;11: 533–536. 8. Abellan van Kan G, Rolland Y, Bergman H, et al. The I.A.N.A. Task Force on frailty assessment of older people in clinical practice. J Nutr Health Aging 2008;12:29–37. 9. Lee M, Chodosh J. Dementia and life expectancy: What do we know? J Am Med Dir Assoc 2009;10:466–471. 10. Morley JE. Alzheimer’s disease: Future treatments. J Am Med Dir 2011; 12:1–7. 11. Kolanowski A, Fick DM, Campbell J, et al. A preliminary study of anticholinergic burden and relationship to a quality of life indicator, engagement in activities, in nursing home residents with dementia. J Am Med Dir Assoc 2009;10:252–257. 12. Olsson J, Bergman A, Carlsten A, et al. Quality of drug prescribing in elderly people in nursing homes and special care units for dementia: A cross-sectional computerized pharmacy register analysis. Clin Drug Investig 2010;30:289–300. 13. Chatterjee S, Mehta S, Sherer JT, et al. Prevalence and predictors of anticholinergic medication use in elderly nursing home residents with dementia: Analysis of data from the 2004 National Nursing Home Survey. Drugs Aging 2010;27:987–997. 14. Lowry E, Woodman RJ, Soiza RL, et al. Clinical and demographic factors associated with antimuscarinic medication use in older hospitalized patients. Hosp Pract (Minneap) 2011;39:30–36. 15. Fitzgerald SP, Bean NG. An analysis of the interactions between individual comorbidities and their treatments—implications for guidelines and polypharmacy. J Am Med Dir Assoc 2010;11:475–484. 16. Gokce Kutsal Y, Barak A, et al. Polypharmacy in the elderly: A multicenter study. J Am Med Dir Assoc 2009;10:486–490. 17. Morley JE. Polypharmacy in the nursing home. J Am Med Dir Assoc 2009;10:289–291. 18. Miles RW. A conversation: Polypharmacy in the nursing home. J Am Med Dir Assoc 2010;11:296–297. 19. Low LF, Anstey KL, Sachdev P. Use of medications with anticholinergic properties and cognitive function in a young-old community sample. Int J Geriatr Psychiatry 2009;24:578–584. 20. Campbell N, Boustani M, Limbil T, et al. The cognitive impact of anticholinergics: A clinical review. Clin Interv Aging 2009;4:225–233. 21. Carriere I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: The 3-City Study. Arch Intern Med 2009;169: 1317–1324.
543.e1 Morley
22. Hori K, Konishi K, Watanabe K, et al. Influence of anticholinergic activity in serum on clinical symptoms of Alzheimer’s disease. Neuropsychobiology 2011;63:147–153. 23. Konishi K, Hori K, Uchida H, et al. Adverse effects of anticholinergic activity on cognitive functions in Alzheimer’s disease. Psychogeriatrics 2010;10:34–38. 24. Sittironnarit G, Ames D, Bush AI, et al. Effects of anticholinergic drugs on cognitive function in older Australians: Results from the AIBL Study. Dement Geriatr Cogni Disord 2011;31:173–178. 25. Uusvaara J, Pitkala KH, Kautiainen H, et al. Association of anticholinergic drugs with hospitalization and mortality among older cardiovascular patients: A prospective study. Drugs Aging 2011;28:131–138. 26. Campbell NL, Boustani MA, Lane KA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology 2010;75:152–159. 27. Uusvaara J, Pitkala KH, Tienari PJ, et al. Association between anticholinergic drugs and apolipoprotein E epsilon4 allele and poorer cognitive function in older cardiovascular patients: a cross-sectional study. J Am Geriatr Soc 2009;57:427–431. 28. Volicer L. Toward better terminology of behavioral symptoms of dementia. J Am Med Dir Assoc 2011. Jan 14 [Epub ahead of print]. 29. Nazir A, Arling G, Perkins AJ, Boustani M. Monitoring quality of care for nursing home Residents with behavioral and psychological symptoms related to dementia. J Am Med Dir Assoc 2010. Dec 29 [Epub ahead of print]. 30. Voyer P, Richard S, McCusker J, et al. Detection of delirium and its symptoms by nurses working in a long-term care facility. J Am Med Dir Assoc 2010. Dec 15 [Epub ahead of print]. 31. Morley JE. Clinical practice in nursing homes as a key for progress. J Nutr Health Aging 2010;14:586–593. 32. Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: A potential risk factor for psychosis onset in Alzheimer’s disease? Exp Opin Drug Saf 2009;8:549–557. 33. Cornege-Blokland E, Kleijer BC, Hertogh CM, et al. Reasons to prescribe antipsychotics for the behavioral symptoms of dementia: A survey in Dutch nursing homes among physicians, nurses, and family caregiver. J Am Med Dir Assoc 2010. Dec 14 [Epub ahead of print]. 34. Lester P, Kohen I, Stefanacci RG, et al. Antipsychotic drug use since the FDA black box warning: Survey of nursing home policies. J Am Med Dir Assoc 2010. Sep 30 [Epub ahead of print]. 35. Jalbert JJ, Eaton CB, Miller SC, et al. Antipsychotic use and the risk of hip fracture among older adults afflicted with dementia. J Am Med Dir Assoc 2010;11:120–127. 36. Cabrera MA, Dellaroza MS, Trelha CS, et al. Psychoactive drugs as risk factors for functional decline among noninstitutionalized dependent elderly people. J Am Med Dir Assoc 2010;11:519–522. 37. Modi A, Weiner M, Craig BA, et al. 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. 38. Robinson M, Rowett D, Leverton A, et al. Changes in utilization of anticholinergic drugs after initiation of cholinesterase inhibitors. Pharmacoepidemiol Drug Saf 2009;18:659–664. 39. Morley JE. Anorexia, weight loss, and frailty. J Am Med Dir Assoc 2010; 11:225–228. 40. Argiles JM, Anker SD, Evans WJ, et al. Consensus on cachexia definitions. J Am Med Dir Assoc 2010;11:229–230. 41. Morley JE. Weight loss in older persons: New therapeutic approaches. Curr Pharm Des 2007;13:3637–3647. 42. Morley JE. Assessment of malnutrition in older persons: A focus on the Mini Nutritional Assessment. J Nutr Health Aging 2011;15:87–90.
JAMDA – October 2011