Skip to main content

Advertisement

SpringerLink
Log in

Use of Medications with Anticholinergic Properties and the Long-Term Risk of Hospitalization for Falls and Fractures in the EPIC-Norfolk Longitudinal Cohort Study

  • Original Research Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

The consumption of medications with anticholinergic activity has been suggested to result in the adverse effects of mental confusion, visual disturbance, and muscle weakness, which may lead to falls. Existing published evidence linking anticholinergic drugs with falls, however, remains weak. This study was conducted to evaluate the relationship between anticholinergic cognitive burden (ACB) and the long-term risk of hospitalization with falls and fractures in a large population study. The dataset comprised information from 25,639 men and women (aged 40–79 years) recruited from 1993 to 1997 from Norfolk, United Kingdom into the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The time to first hospital admission with a fall with or without fracture was obtained from the National Health Service hospital information system. Cox-proportional hazards analyses were conducted to adjust for confounders and competing risks. The fall hospitalization rate was 5.8% over a median follow-up of ~ 19.4 years. The unadjusted incidence rate ratio for the use of any drugs with anticholinergic properties was 1.79 (95% CI 1.66–1.93). The hazard ratios (95% CI) for ACB scores of 1, 2–3, and ≥ 4 compared with ACB = 0 for fall hospitalization were 1.20 (1.09–1.33), 1.42 (1.25–1.60), and 1.39 (1.21–1.60) after adjustment for age, gender, medical conditions, physical activity, and blood pressure. Medications with anticholinergic activity are associated with an increased risk of subsequent hospitalization with a fall over a 19-year follow-up period. The biological mechanisms underlying the long-term risk of hospitalization with a fall or fracture following baseline ACB exposure remains unclear and requires further evaluation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kwan MM, Close JC, Wong AK, Lord SR. Falls incidence, risk factors, and consequences in Chinese older people: a systematic review. J Am Geriatr Soc. 2011;59(3):536–43. https://doi.org/10.1111/j.1532-5415.2010.03286.x.

    Article  PubMed  Google Scholar 

  2. Masud T, Morris RO. Epidemiology of falls. Age Ageing. 2001;30(Suppl 4):3–7.

    Article  Google Scholar 

  3. Ambrose AF, Paul G, Hausdorff JM. Risk factors for falls among older adults: a review of the literature. Maturitas. 2013;75(1):51–61. https://doi.org/10.1016/j.maturitas.2013.02.009.

    Article  PubMed  Google Scholar 

  4. Chang HT, Chen HC, Chou P. Factors associated with fear of falling among community-dwelling older adults in the Shih-Pai study in Taiwan. PLoS One. 2016;11(3):e0150612. https://doi.org/10.1371/journal.pone.0150612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nishtala PS, Salahudeen MS, Hilmer SN. Anticholinergics: theoretical and clinical overview. Expert Opin Drug Saf. 2016;15(6):753–68. https://doi.org/10.1517/14740338.2016.1165664.

    Article  CAS  PubMed  Google Scholar 

  6. Collamati A, Martone AM, Poscia A, Brandi V, Celi M, Marzetti E, et al. Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence. Aging Clin Exp Res. 2016;28(1):25–35. https://doi.org/10.1007/s40520-015-0359-7.

    Article  PubMed  Google Scholar 

  7. Kidd AC, Musonda P, Soiza RL, Butchart C, Lunt CJ, Pai Y, et al. The relationship between total anticholinergic burden (ACB) and early in-patient hospital mortality and length of stay in the oldest old aged 90 years and over admitted with an acute illness. Arch Gerontol Geriatr. 2014;59(1):155–61. https://doi.org/10.1016/j.archger.2014.01.006.

    Article  CAS  PubMed  Google Scholar 

  8. Rojas-Fernandez CH, Seymour N, Brown SG. Helping pharmacists to reduce fall risk in long-term care: a clinical tool to facilitate the medication review process. Can Pharm J (Ott). 2014;147(3):171–8. https://doi.org/10.1177/1715163514529706.

    Article  PubMed Central  Google Scholar 

  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. https://doi.org/10.1016/j.maturitas.2015.10.009.

    Article  PubMed  Google Scholar 

  10. 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. https://doi.org/10.1111/jgs.13543.

    Article  PubMed  Google Scholar 

  11. 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. https://doi.org/10.1177/1060028015596998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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. https://doi.org/10.1097/jcp.0000000000000195.

    Article  CAS  PubMed  Google Scholar 

  13. Suehs BT, Caplan EO, Hayden J, Ng DB, Gaddy RR. The relationship between anticholinergic exposure and falls, fractures, and mortality in patients with overactive bladder. Drugs Aging. 2019;36(10):957–67. https://doi.org/10.1007/s40266-019-00694-5.

    Article  CAS  PubMed  Google Scholar 

  14. Green AR, Reifler LM, Bayliss EA, Weffald LA, Boyd CM. 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. Drugs Aging. 2019;36(3):289–97. https://doi.org/10.1007/s40266-018-00630-z.

    Article  CAS  PubMed  Google Scholar 

  15. Carrière I, Fourrier-Reglat A, Dartigues J-F, Rouaud O, Pasquier F, Ritchie K, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317–24. https://doi.org/10.1001/archinternmed.2009.229.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic drug exposure and the risk of dementia: a nested case–control study. JAMA Intern Med. 2019. https://doi.org/10.1001/jamainternmed.2019.0677.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Myint PK, Fox C, Kwok CS, Luben RN, Wareham NJ, Khaw KT. Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population study. Age Ageing. 2015;44(2):219–25. https://doi.org/10.1093/ageing/afu185.

    Article  PubMed  Google Scholar 

  18. Day N, Oakes S, Luben R, Khaw KT, Bingham S, Welch A, et al. EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer. 1999;80(Suppl 1):95–103.

    PubMed  Google Scholar 

  19. Shohaimi S, Luben R, Wareham N, Day N, Bingham S, Welch A, et al. Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk). J Epidemiol Community Health. 2003;57(4):270–6.

    Article  CAS  Google Scholar 

  20. Wareham NJ, Jakes RW, Rennie KL, Schuit J, Mitchell J, Hennings S, et al. Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr. 2003;6(4):407–13. https://doi.org/10.1079/phn2002439.

    Article  PubMed  Google Scholar 

  21. Boustani M, Campbell N, Munger S, Maidment I, Fox C. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008. https://doi.org/10.2217/1745509X.4.3.311.

    Article  Google Scholar 

  22. Hsu WH, Wen YW, Chen LK, Hsiao FY. Comparative associations between measures of anti-cholinergic burden and adverse clinical outcomes. Ann Fam Med. 2017;15(6):561–9. https://doi.org/10.1370/afm.2131.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lozano-Ortega G, Johnston KM, Cheung A, Wagg A, Campbell NL, Dmochowski RR, et al. A review of published anticholinergic scales and measures and their applicability in database analyses. Arch Gerontol Geriatr. 2019. https://doi.org/10.1016/j.archger.2019.05.010.

    Article  PubMed  Google Scholar 

  24. Sinha S, Myint PK, Luben RN, Khaw KT. Accuracy of death certification and hospital record linkage for identification of incident stroke. BMC Med Res Methodol. 2008;8:74. https://doi.org/10.1186/1471-2288-8-74.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 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;16:76. https://doi.org/10.1186/s12877-016-0251-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fox C, Richardson K, Maidment ID, Savva GM, Matthews FE, Smithard D, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011;59(8):1477–83. https://doi.org/10.1111/j.1532-5415.2011.03491.x.

    Article  PubMed  Google Scholar 

  27. Ablett AD, Wood AD, Barr R, Guillot J, Black AJ, Macdonald HM, et al. A high anticholinergic burden is associated with a history of falls in the previous year in middle-aged women: findings from the Aberdeen prospective osteoporosis screening study. Ann Epidemiol. 2018;28(8):557–62. https://doi.org/10.1016/j.annepidem.2018.05.011(e2).

    Article  PubMed  Google Scholar 

  28. Hanlon JT, Zhao X, Naples JG, Aspinall SL, Perera S, Nace DA, et al. Central nervous system medication burden and serious falls in older nursing home residents. J Am Geriatr Soc. 2017;65(6):1183–9. https://doi.org/10.1111/jgs.14759.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 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. https://doi.org/10.1007/s40266-015-0298-1.

    Article  CAS  PubMed  Google Scholar 

  30. Tan MP, Kamaruzzaman SB, Zakaria MI, Chin AV, Poi PJ. Ten-year mortality in older patients attending the emergency department after a fall. Geriatr Gerontol Int. 2016;1:111–7. https://doi.org/10.1111/ggi.12446.

    Article  Google Scholar 

  31. Zia A, Kamaruzzaman SB, Myint PK, Tan MP. The association of antihypertensives with postural blood pressure and falls among seniors residing in the community: a case–control study. Eur J Clin Investig. 2015;45(10):1069–76. https://doi.org/10.1111/eci.12508.

    Article  CAS  Google Scholar 

  32. Naples JG, Marcum ZA, Perera S, Gray SL, Newman AB, Simonsick EM, et al. Concordance between anticholinergic burden scales. J Am Geriatr Soc. 2015;63(10):2120–4. https://doi.org/10.1111/jgs.13647.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research.

Author information

Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Maw Pin Tan, Guo Jeng Tan & Sumaiyah Mat

  2. Ageing and Age-Associated Disorders Research Group, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    Maw Pin Tan, Guo Jeng Tan & Sumaiyah Mat

  3. Department of Medical Sciences, Faculty of Healthcare and Medical Sciences, Sunway University, Bandar Sunway, Malaysia

    Maw Pin Tan

  4. Clinical Gerontology Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK

    Robert N. Luben, Kay-Tee Khaw & Phyo Kyaw Myint

  5. MRC Epidemiology Unit, Cambridge, UK

    Nicholas J. Wareham

  6. Ageing Clinical and Experimental Research (ACER) Team, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK

    Phyo Kyaw Myint

Authors
  1. Maw Pin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guo Jeng Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sumaiyah Mat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert N. Luben
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas J. Wareham
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kay-Tee Khaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Phyo Kyaw Myint
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Maw Pin Tan or Phyo Kyaw Myint.

Ethics declarations

Conflict of interest

The authors Maw Pin Tan, Guo Jeng Tan, Sumaiyah Mat, Robert N. Luben, Nicholas J. Wareham, Kay-Tee Khaw, and Phyo Kyaw Myint have no conflicts of interest that are directly relevant to the content of this work.

Funding

This work was supported by grants from the Medical Research Council and Cancer Research UK. Funders had no role in study design or interpretation of the findings.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Norwich Local Research Ethics Committee + 05/Q0101/191) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, M.P., Tan, G.J., Mat, S. et al. Use of Medications with Anticholinergic Properties and the Long-Term Risk of Hospitalization for Falls and Fractures in the EPIC-Norfolk Longitudinal Cohort Study. Drugs Aging 37, 105–114 (2020). https://doi.org/10.1007/s40266-019-00731-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-019-00731-3

Search

Navigation