Drugs & Aging

, Volume 36, Issue 3, pp 289–297 | Cite as

Drugs Contributing to Anticholinergic Burden and Risk of Fall or Fall-Related Injury among Older Adults with Mild Cognitive Impairment, Dementia and Multiple Chronic Conditions: A Retrospective Cohort Study

  • Ariel R. GreenEmail author
  • Liza M. Reifler
  • Elizabeth A. Bayliss
  • Linda A. Weffald
  • Cynthia M. BoydEmail author
Original Research Article



It is not known whether drugs with different anticholinergic ratings contribute proportionately to overall anticholinergic score.


Our objective was to assess the risk of falls or fall-related injuries as a function of the overall anticholinergic score resulting from drugs with different anticholinergic ratings among people with impaired cognition.


This was a retrospective cohort study of adults aged  ≥ 65 years with mild cognitive impairment (MCI) or dementia and two or more additional chronic conditions (N = 10,698) in an integrated delivery system. Electronic health record data, including pharmacy fills and diagnosis claims, were used to assess anticholinergic medication use, quantified using the anticholinergic cognitive burden (ACB) scale, falls and fall-related injuries.


During a median follow-up of 366 days, 63% of the cohort used one or more ACB drug; 2015 (18.8%) people experienced a fall or fall-related injury. Among patients with a daily ACB score of 5, the greatest increase in risk of falls or fall-related injuries was seen when level 2 and level 3 drugs were used in combination [hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.51–2.83]. Multiple ACB level 1 drugs taken together also increased the hazard of a fall or fall-related injury (HR 1.16; 95% CI 1.03–1.32). The risk of fall or fall-related injury as a function of exposure to ACB level 2 drugs (HR 1.56; 95% CI 1.16–2.10) was higher than that for ACB level 1 or 3 drugs.


The same daily ACB score was associated with a different degree of risk, depending on the ACB ratings of the individual drugs comprising the score. Combinations of level 2 and level 3 drugs had the greatest risk of fall or fall-related injury relative to other individuals with the same daily ACB score. Low-potency anticholinergic drugs taken together modestly increased the hazard of a fall or fall-related injury.



This study was supported by R24AG045050-03S2 from the National Institute on Aging. Support was provided by the KPCO Pharmacy Department for Linda Weffald’s time. Dr. Boyd’s time was in part supported by 1K24AG056578-01 from the National Institute on Aging. Dr. Green is supported by K23AG054742.

Compliance with Ethical Standards

Conflict of Interest

Ariel Green, Liza Reifler, Elizabeth Bayliss, Linda A. Weffald have no conflicts of interest that are directly relevant to the content of this study. Cynthia Boyd writes a chapter on multimorbidity for UpToDate, for which she receives a royalty.

Supplementary material

40266_2018_630_MOESM1_ESM.pdf (218 kb)
Supplementary material 1 (pdf 217 kb)


  1. 1.
    American Geriatrics Society. Updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46. Scholar
  2. 2.
    Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000;93(9):457–62.CrossRefGoogle Scholar
  3. 3.
    Wilson NM, Hilmer SN, March LM, Cameron ID, Lord SR, Seibel MJ, et al. Associations between drug burden index and falls in older people in residential aged care. J Am Geriatr Soc. 2011;59(5):875–80.CrossRefGoogle Scholar
  4. 4.
    Nishtala PS, Narayan SW, Wang T, Hilmer SN. Associations of drug burden index with falls, general practitioner visits, and mortality in older people. Pharmacoepidemiol Drug Saf. 2014;23(7):753–8.CrossRefGoogle Scholar
  5. 5.
    Dauphinot V, Faure R, Omrani S, Goutelle S, Bourguignon L, Krolak-Salmon P, et al. Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an elderly inpatient, multicenter cohort. J Clin Psychopharmacol. 2014;34(5):565–70.CrossRefGoogle Scholar
  6. 6.
    Aizenberg D, Sigler M, Weizman A, Barak Y. Anticholinergic burden and the risk of falls among elderly psychiatric inpatients: a 4-year case-control study. Int Psychogeriatr. 2002;14(3):307–10.CrossRefGoogle Scholar
  7. 7.
    Marcum ZA, Perera S, Thorpe JM, Switzer GE, Gray SL, Castle NG, et al. Anticholinergic use and recurrent falls in community-dwelling older adults: findings from the Health ABC study. Ann Pharmacother. 2015;49(11):1214–21.CrossRefGoogle Scholar
  8. 8.
    Richardson K, Bennett K, Maidment ID, Fox C, Smithard D, Kenny RA. Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults. J Am Geriatr Soc. 2015;63(8):1561–9.CrossRefGoogle Scholar
  9. 9.
    Zia A, Kamaruzzaman S, Myint PK, Tan MP. Anticholinergic burden is associated with recurrent and injurious falls in older individuals. Maturitas. 2016;84:32–7.CrossRefGoogle Scholar
  10. 10.
    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.CrossRefGoogle Scholar
  11. 11.
    Salahudeen MS, Duffull SB, Nishtala PS. Impact of anticholinergic discontinuation on cognitive outcomes in older people: a systematic review. Drugs Aging. 2014;31(3):185–92.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.CrossRefGoogle Scholar
  13. 13.
    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.Google Scholar
  14. 14.
    Agency for Healthcare Research and Quality. Chronic condition classification. Accessed 14 Aug 2017.
  15. 15.
    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.CrossRefGoogle Scholar
  16. 16.
    Campbell NL, Maidment I, Fox C, Khan B, Boustani M. The 2012 update to the anticholinergic cognitive burden scale. J Am Geriatr Soc. 2013;61(S1):S142–3.Google Scholar
  17. 17.
    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.CrossRefGoogle Scholar
  18. 18.
    Hoffman GJ, Hays RD, Shapiro MF, Wallace SP, Ettner SL. Claims-based Identification methods and the cost of fall-related injuries among US older adults. Med Care. 2016;54(7):664–71.CrossRefGoogle 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.CrossRefGoogle Scholar
  20. 20.
    Nilsson M, Eriksson J, Larsson B, Oden A, Johansson H, Lorentzon M. fall risk assessment predicts fall-related injury, hip fracture, and head injury in older adults. J Am Geriatr Soc. 2016;64(11):2242–50.CrossRefGoogle Scholar
  21. 21.
    Beydoun HA, Beydoun MA, Mishra NK, Rostant OS, Zonderman AB, Eid SM. Comorbid Parkinson’s disease, falls and fractures in the 2010 National Emergency Department Sample. Parkinsonism Relat Disord. 2017;35:30–5.CrossRefGoogle Scholar
  22. 22.
    Berdot S, Bertrand M, Dartigues JF, Fourrier A, Tavernier B, Ritchie K, et al. Inappropriate medication use and risk of falls—a prospective study in a large community-dwelling elderly cohort. BMC Geriatr. 2009;9:30.CrossRefGoogle Scholar
  23. 23.
    Alvarez CA, Mortensen EM, Makris UE, Berlowitz DR, Copeland LA, Good CB, et al. Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study. BMC Geriatr. 2015;15(1):2.CrossRefGoogle Scholar
  24. 24.
    Marcum ZA, Wirtz HS, Pettinger M, LaCroix AZ, Carnahan R, Cauley JA, et al. Anticholinergic medication use and falls in postmenopausal women: findings from the women’s health initiative cohort study. BMC Geriatr. 2016;16(1):76.CrossRefGoogle Scholar
  25. 25.
    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.CrossRefGoogle Scholar
  26. 26.
    Fraser LA. Effect of anticholinergic medications on falls, fracture risk, and bone mineral density over a 10-year period. Ann Pharmacother. 2014;48(8):954–61.CrossRefGoogle Scholar
  27. 27.
    Kao LT, Huang CY, Lin HC, Chu CM. No increased risk of fracture in patients receiving antimuscarinics for overactive bladder syndrome: a retrospective cohort study. J Clin Pharmacol. 2018;58(6):727–32.CrossRefGoogle Scholar
  28. 28.
    Marcum ZA, Wirtz HS, Pettinger M, LaCroix AZ, Carnahan R, Cauley JA, et al. Anticholinergic medication use and fractures in postmenopausal women: findings from the women’s health initiative. Drugs Aging. 2015;32(9):755–63.CrossRefGoogle Scholar
  29. 29.
    Moga DC, Carnahan RM, Lund BC, Pendergast JF, Wallace RB, Torner JC, et al. Risks and benefits of bladder antimuscarinics among elderly residents of Veterans Affairs Community Living Centers. J Am Med Dir Assoc. 2013;14(10):749–60.CrossRefGoogle Scholar
  30. 30.
    Lackner TE, Wyman JF, McCarthy TC, Monigold M, Davey C. Randomized, placebo-controlled trial of the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired nursing home residents with urge urinary incontinence. J Am Geriatr Soc. 2008;56(5):862–70.CrossRefGoogle Scholar
  31. 31.
    Hanlon JT, Semla TP, Schmader KE. Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug-disease interactions in the elderly quality measures. J Am Geriatr Soc. 2015;63(12):e8–18.CrossRefGoogle Scholar
  32. 32.
    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.CrossRefGoogle Scholar
  33. 33.
    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.CrossRefGoogle Scholar
  34. 34.
    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.CrossRefGoogle Scholar
  35. 35.
    Green AR, Reifler LM, Boyd CM, Weffald LA, Bayliss EA. Medication profiles of patients with cognitive impairment and high anticholinergic burden. Drugs Aging. 2018;35(3):223–32.CrossRefGoogle Scholar
  36. 36.
    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.CrossRefGoogle Scholar
  37. 37.
    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.CrossRefGoogle Scholar
  38. 38.
    Mold JW, Hamm RM, McCarthy LH. The law of diminishing returns in clinical medicine: how much risk reduction is enough? J Am Board Fam Med. 2010;23(3):371–5.CrossRefGoogle Scholar
  39. 39.
    Sonnenberg A. Diminishing returns in sequential interventions of gastroenterology. Eur J Gastroenterol Hepatol. 2008;20(5):465–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

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 Family MedicineUniversity of Colorado School of MedicineAuroraUSA
  4. 4.University of Colorado Skaggs School of Pharmacy and Pharmaceutical SciencesAuroraUSA
  5. 5.Department of Health Policy and ManagementJohns Hopkins University Bloomberg School of Public HealthBaltimoreUSA

Personalised recommendations