Drugs & Aging

, Volume 35, Issue 3, pp 223–232 | Cite as

Medication Profiles of Patients with Cognitive Impairment and High Anticholinergic Burden

short communication

Abstract

Background

Drugs with anticholinergic properties are considered potentially inappropriate in patients with cognitive impairment because harms—including delirium, falls, and fractures—may outweigh benefits.

Objective

To highlight opportunities to improve clinical decision making and care for patients with cognitive impairment and multiple chronic conditions, we identified distinct subgroups of patients with mild cognitive impairment (MCI) and dementia who had high cumulative anticholinergic burden and specific patterns of anticholinergic use.

Patients and Methods

We conducted a retrospective cohort study in a not-for-profit, integrated delivery system. Participants included community-dwelling adults aged 65 years and older (n = 13,627) with MCI or dementia and at least two other chronic diseases. We calculated the Anticholinergic Cognitive Burden (ACB) score for each participant from pharmacy and electronic health record (EHR) data. Among individuals with a mean 12-month ACB score ≥ 2, we used agglomerative hierarchical clustering to identify groups or clusters of individuals with similar anticholinergic prescription patterns.

Results

Twenty-four percent (3257 participants) had high anticholinergic burden, defined as an ACB score ≥ 2. Clinically meaningful clusters based upon anchoring medications or drug classes included a cluster of cardiovascular medications (n = 1497; 46%); two clusters of antidepressant medications (n = 633; 20%); and a cluster based on use of bladder antimuscarinics (n = 431; 13%). Several clusters comprised multiple central nervous system (CNS)-active drugs.

Conclusions

Cardiovascular and CNS-active medications comprise a substantial portion of anticholinergic burden in people with cognitive impairment and multiple chronic conditions. Antidepressants were highly prevalent. Clinical profiles elucidated by these clusters of anticholinergic medications can inform targeted approaches to care.

Notes

Compliance with Ethical Standards

Funding

This study was supported by R24AG045050-03S2 from the National Institute on Aging. Support was provided by Kaiser Permanente Colorado Pharmacy Department for Linda Weffald’s time. Ariel Green's time was partially supported by K23AG054742-01A1 from the National Institute on Aging.

Conflicts of interest

Dr. Boyd writes a chapter on multimorbidity for UpToDate, for which she receives a royalty. ARG, LMR, LAW, and EAB declare that they have no conflicts of interest relevant to the content of this study.

Supplementary material

40266_2018_522_MOESM1_ESM.docx (22 kb)
Online Resource 1: ICD-9 and ICD-10 codes used to identify patients with mild cognitive impairment and dementia (DOCX 22 kb)
40266_2018_522_MOESM2_ESM.docx (77 kb)
Online Resource 2: Further detail about agglomerative hierarchical clustering method (DOCX 76 kb)

References

  1. 1.
    Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology. 2013;80(19):1778–83.  https://doi.org/10.1212/wnl.0b013e31828726f5.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Campbell NL, Boustani MA. Adverse cognitive effects of medications: turning attention to reversibility. JAMA Intern Med. 2015;175(3):408–9.  https://doi.org/10.1001/jamainternmed.2014.7667.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Association Alzheimer’s. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement. 2017;13(4):325–73.  https://doi.org/10.1016/j.jalz.2017.02.001.CrossRefGoogle Scholar
  4. 4.
    Lin PJ, Zhong Y, Fillit HM, Chen E, Neumann PJ. Medicare expenditures of individuals with Alzheimer’s Disease and related dementias or mild cognitive impairment before and after diagnosis. J Am Geriatr Soc. 2016;64(8):1549–57.  https://doi.org/10.1111/jgs.14227.CrossRefPubMedGoogle Scholar
  5. 5.
    Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294(6):716–24.  https://doi.org/10.1001/jama.294.6.716.CrossRefPubMedGoogle Scholar
  6. 6.
    Hinton L, Franz CE, Reddy G, Flores Y, Kravitz RL, Barker JC. Practice constraints, behavioral problems, and dementia care: primary care physicians’ perspectives. J Gen Intern Med. 2007;22(11):1487–92.  https://doi.org/10.1007/s11606-007-0317-y.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lin P-J, Zhong Y, Fillit HM, Chen E, Neumann PJ. Medicare expenditures of individuals with Alzheimer’s disease and related dementias or mild cognitive impairment before and after diagnosis. J Am Geriatr Soc. 2016;64(8):1549–57.  https://doi.org/10.1111/jgs.14227.CrossRefPubMedGoogle Scholar
  8. 8.
    Lin PJ, Fillit HM, Cohen JT, Neumann PJ. Potentially avoidable hospitalizations among Medicare beneficiaries with Alzheimer’s disease and related disorders. Alzheimers Dement. 2013;9(1):30–8.  https://doi.org/10.1016/j.jalz.2012.11.002.CrossRefPubMedGoogle Scholar
  9. 9.
    Chatterjee S, Bali V, Carnahan RM, Chen H, Johnson ML, Aparasu RR. Risk of mortality associated with anticholinergic use in elderly nursing home residents with depression. Drugs Aging. 2017.  https://doi.org/10.1007/s40266-017-0475-5.PubMedGoogle Scholar
  10. 10.
    Chatterjee S, Bali V, Carnahan RM, Chen H, Johnson ML, Aparasu RR. Anticholinergic medication use and risk of fracture in elderly adults with depression. J Am Geriatr Soc. 2016;64(7):1492–7.  https://doi.org/10.1111/jgs.14182.CrossRefPubMedGoogle Scholar
  11. 11.
    American Geriatrics Society. Updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46.  https://doi.org/10.1111/jgs.13702.CrossRefGoogle Scholar
  12. 12.
    Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.  https://doi.org/10.1001/jamainternmed.2014.7663.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332(7539):455–9.  https://doi.org/10.1136/bmj.38740.439664.de.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Campbell NL, Unverzagt F, LaMantia MA, Khan BA, Boustani MA. Risk factors for the progression of mild cognitive impairment to dementia. Clin Geriatr Med. 2013;29(4):873–93.  https://doi.org/10.1016/j.cger.2013.07.009.CrossRefPubMedGoogle Scholar
  15. 15.
    Campbell N, Boustani M, Limbil T, Ott C, Fox C, Maidment I, et al. The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging. 2009;4:225–33.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Agency for Healthcare Research and Quality. Chronic Condition Classification. http://www.icpsr.umich.edu/icpsrweb/content/AHRQMCC/shared-code.html. Accessed 14 August 2017.
  17. 17.
    Amjad H, Carmichael D, Austin AM, Chang CH, Bynum JP. Continuity of Care and Health Care Utilization in Older Adults With Dementia in Fee-for-Service Medicare. JAMA Intern Med. 2016;176(9):1371–8.  https://doi.org/10.1001/jamainternmed.2016.3553.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cardwell K, Hughes CM, Ryan C. The association between anticholinergic medication burden and health related outcomes in the ‘Oldest Old’: a systematic review of the literature. Drugs Aging. 2015;32(10):835–48.  https://doi.org/10.1007/s40266-015-0310-9.CrossRefPubMedGoogle Scholar
  19. 19.
    Salahudeen MS, Hilmer SN, Nishtala PS. Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people. J Am Geriatr Soc. 2015;63(1):85–90.  https://doi.org/10.1111/jgs.13206.CrossRefPubMedGoogle Scholar
  20. 20.
    Campbell NL, Boustani MA, Lane KA, Gao S, Hendrie H, Khan BA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology. 2010;75(2):152–9.  https://doi.org/10.1212/wnl.0b013e3181e7f2ab.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Campbell NL, Perkins AJ, Bradt P, Perk S, Wielage RC, Boustani MA, et al. Association of anticholinergic burden with cognitive impairment and health care utilization among a diverse ambulatory older adult population. Pharmacotherapy. 2016;36(11):1123–31.  https://doi.org/10.1002/phar.1843.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Bhattacharya R, Chatterjee S, Carnahan RM, Aparasu RR. Prevalence and predictors of anticholinergic agents in elderly outpatients with dementia. Am J Geriatr Pharmacother. 2011;9(6):434–41.  https://doi.org/10.1016/j.amjopharm.2011.10.001.CrossRefPubMedGoogle Scholar
  23. 23.
    Chatterjee S, Mehta S, Sherer JT, Aparasu RR. 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(12):987–97.  https://doi.org/10.2165/11584430-000000000-00000.CrossRefPubMedGoogle Scholar
  24. 24.
    Marengoni A, Rizzuto D, Wang HX, Winblad B, Fratiglioni L. Patterns of chronic multimorbidity in the elderly population. J Am Geriatr Soc. 2009;57(2):225–30.  https://doi.org/10.1111/j.1532-5415.2008.02109.x.CrossRefPubMedGoogle Scholar
  25. 25.
    Goldstein G, Luther JF, Jacoby AM, Haas GL, Gordon AJ. A taxonomy of medical comorbidity for veterans who are homeless. J Health Care Poor Underserved. 2008;19(3):991–1005.  https://doi.org/10.1353/hpu.0.0040.CrossRefPubMedGoogle Scholar
  26. 26.
    Newcomer SR, Steiner JF, Bayliss EA. Identifying subgroups of complex patients with cluster analysis. Am J Manag Care. 2011;17(8):e324–32.PubMedGoogle Scholar
  27. 27.
    Shaukat A, Habib A, Lane KA, Shen C, Khan S, Hellman YM, et al. Anticholinergic medications: an additional contributor to cognitive impairment in the heart failure population? Drugs Aging. 2014;31(10):749–54.  https://doi.org/10.1007/s40266-014-0204-2.CrossRefPubMedGoogle Scholar
  28. 28.
    Parkinson L, Magin PJ, Thomson A, Byles JE, Caughey GE, Etherton-Beer C, et al. Anticholinergic burden in older women: not seeing the wood for the trees? Med J Aust. 2015;202(2):91–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Green AR, Oh E, Hilson L, Tian J, Boyd CM. Anticholinergic burden in older adults with mild cognitive impairment. J Am Geriatr Soc. 2016;64(12):e313–4.  https://doi.org/10.1111/jgs.14554.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gerlach LB, Olfson M, Kales HC, Maust DT. Opioids and Other Central Nervous System-Active Polypharmacy in Older Adults in the United States. J Am Geriatr Soc. 2017.  https://doi.org/10.1111/jgs.14930.PubMedGoogle Scholar
  31. 31.
    Bhattacharjee S, Oh YM, Reiman EM, Burke WJ. Prevalence, Patterns, and Predictors of Depression Treatment among Community-Dwelling Elderly Individuals with Dementia in the United States. Am J Geriatr Psychiatry. 2017;25(7):803–13.  https://doi.org/10.1016/j.jagp.2017.03.003.CrossRefPubMedGoogle Scholar
  32. 32.
    Rosenberg PB, Mielke MM, Han D, Leoutsakos JS, Lyketsos CG, Rabins PV, et al. The association of psychotropic medication use with the cognitive, functional, and neuropsychiatric trajectory of Alzheimer’s disease. Int J Geriatr Psychiatry. 2012;27(12):1248–57.  https://doi.org/10.1002/gps.3769.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Orgeta V, Qazi A, Spector AE. Orrell M (2014) Psychological treatments for depression and anxiety in dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2014;1:CD009125.  https://doi.org/10.1002/14651858.cd009125.pub2.Google Scholar
  34. 34.
    Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577–85.  https://doi.org/10.1111/j.1532-5415.2011.03355.x.CrossRefPubMedGoogle Scholar
  35. 35.
    Palmer JB, Albrecht JS, Park Y, Dutcher S, Rattinger GB, Simoni-Wastila L, et al. Use of drugs with anticholinergic properties among nursing home residents with dementia: a national analysis of Medicare beneficiaries from 2007 to 2008. Drugs Aging. 2015;32(1):79–86.  https://doi.org/10.1007/s40266-014-0227-8.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kolanowski A, Fick DM, Campbell J, Litaker M, Boustani M. 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(4):252–7.  https://doi.org/10.1016/j.jamda.2008.11.005.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Carnahan RM, Lund BC, Perry PJ, Pollock BG, Culp KR. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46(12):1481–6.  https://doi.org/10.1177/0091270006292126.CrossRefPubMedGoogle Scholar
  38. 38.
    Sattler EL, Lee JS, Perri M 3rd. Medication (re)fill adherence measures derived from pharmacy claims data in older Americans: a review of the literature. Drugs Aging. 2013;30(6):383–99.  https://doi.org/10.1007/s40266-013-0074-z.CrossRefPubMedGoogle Scholar
  39. 39.
    Ostbye T, Taylor DH Jr, Clipp EC, Scoyoc LV, Plassman BL. Identification of dementia: agreement among national survey data, medicare claims, and death certificates. Health Serv Res. 2008;43(1 Pt 1):313–26.  https://doi.org/10.1111/j.1475-6773.2007.00748.x.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Sachdev PS, Lipnicki DM, Kochan NA, Crawford JD, Thalamuthu A, Andrews G, et al. The prevalence of mild cognitive impairment in diverse geographical and Ethnocultural regions: the COSMIC collaboration. PLoS One. 2015;10(11):e0142388.  https://doi.org/10.1371/journal.pone.0142388.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ward A, Arrighi HM, Michels S, Cedarbaum JM. Mild cognitive impairment: disparity of incidence and prevalence estimates. Alzheimers Dement. 2012;8(1):14–21.  https://doi.org/10.1016/j.jalz.2011.01.002.CrossRefPubMedGoogle Scholar
  42. 42.
    Langa KM, Larson EB, Crimmins EM, Faul JD, Levine DA, Kabeto MU, et al. A comparison of the prevalence of dementia in the United States in 2000 and 2012. JAMA Intern Med. 2017;177(1):51–8.  https://doi.org/10.1001/jamainternmed.2016.6807.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Matlow JN, Bronskill SE, Gruneir A, Bell CM, Stall NM, Herrmann N, et al. Use of Medications of Questionable Benefit at the End of Life in Nursing Home Residents with Advanced Dementia. J Am Geriatr Soc. 2017;65(7):1535–42.  https://doi.org/10.1111/jgs.14844.CrossRefPubMedGoogle Scholar
  44. 44.
    Reppas-Rindlisbacher CE, Fischer HD, Fung K, Gill SS, Seitz D, Tannenbaum C, et al. anticholinergic drug burden in persons with dementia taking a cholinesterase inhibitor: the effect of multiple physicians. J Am Geriatr Soc. 2016;64(3):492–500.  https://doi.org/10.1111/jgs.14034.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sachs GA, Carter R, Holtz LR, Smith F, Stump TE, Tu W, et al. Cognitive impairment: an independent predictor of excess mortality: a cohort study. Ann Intern Med. 2011;155(5):300–8.  https://doi.org/10.7326/0003-4819-155-5-201109060-00007.CrossRefPubMedGoogle Scholar
  46. 46.
    Holmes HM, Min LC, Yee M, Varadhan R, Basran J, Dale W, et al. Rationalizing prescribing for older patients with multimorbidity: considering time to benefit. Drugs Aging. 2013;30(9):655–66.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Geriatric Medicine and GerontologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Institute for Health ResearchKaiser Permanente ColoradoDenverUSA
  3. 3.Department of Health Policy and ManagementJohns Hopkins University Bloomberg School of Public HealthBaltimoreUSA
  4. 4.University of Colorado, Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraUSA
  5. 5.Department of Family MedicineUniversity of Colorado School of MedicineAuroraUSA

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