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Drugs & Aging

, Volume 36, Issue 1, pp 85–91 | Cite as

Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study

  • Luca Pasina
  • Lorenzo Colzani
  • Laura Cortesi
  • Mauro Tettamanti
  • Antonella Zambon
  • Alessandro Nobili
  • Andrea Mazzone
  • Paolo Mazzola
  • Giorgio Annoni
  • Giuseppe Bellelli
Original Research Article

Abstract

Background

Delirium is a neuropsychiatric syndrome which occurs on average in one out of five hospitalized older patients. It is associated with a number of negative outcomes, including worsening of cognitive and functional status, increasing the burden on patients and caregivers, and elevated mortality. Medications with anticholinergic effect have been associated with the clinical severity of delirium symptoms in older medical inpatients, but this association is still debated.

Objective

The aim was to assess the association between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium.

Methods

This retrospective, cross-sectional study was conducted in a sample of older patients admitted to the Acute Geriatric Unit (AGU) of the San Gerardo Hospital in Monza (Italy) between June 2014 and January 2015. Delirium was diagnosed on admission using the 4 ‘A’s Test (4AT), a validated screening tool for delirium diagnosis, which has shown good sensitivity and specificity to detect this condition in elderly patients admitted to an AGU. Each patient’s anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale, a ranking of anticholinergic medications to predict the risk of adverse effects on the central nervous system in older patients.

Results

Of the 477 eligible for the analysis, 151 (31.7%) had delirium. According to the ACB scale, 377 patients (79.0%) received at least one anticholinergic drug. Apart from quetiapine, which has a strong anticholinergic effect, the most commonly prescribed anticholinergic medications had potential anticholinergic effects but unknown clinically relevant cognitive effects according to the ACB scale (score 1). Patients with delirium had a higher anticholinergic burden than those without delirium, with a dose–effect relationship between total ACB score and delirium, which was significant at univariate analysis. A plateau risk was found in patients who scored 0–2, but patients who scored 3 or more had about three or six times the risk of delirium than those not taking anticholinergic drugs. The dose–response relationship was maintained in the multivariate model adjusted for age and sex [odds ratio (OR) 5.88, 95% confidence interval (CI) 2.10–16.60, p = 0.00007], while there was only a non-significant trend in the models adjusted also for dementia and Mini Nutritional Assessment (OR 2.73, 95% CI 0.85–8.77, p = 0.12).

Conclusions

Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity. However, this effect was no longer evident in multivariable logistic regression analysis, after adjustment for dementia and malnutrition. Larger, multicenter studies are required to clarify the complex relationship between drugs, anticholinergic burden and delirium in various categories of hospitalized older patients, including those with dementia and malnutrition.

Notes

Acknowledgements

We are grateful to J.D. Baggott for editorial assistance.

Compliance with Ethical Standards

Funding

No funding sources were used in the conduct of this study or the preparation of this article.

Conflict of interest

Luca Pasina, Lorenzo Colzani, Laura Cortesi, Mauro Tettamanti, Antonella Zambon, Alessandro Nobili, Andrea Mazzone, Paolo Mazzola, Giorgio Annoni and Giuseppe Bellelli have no conflicts of interest that are directly relevant to the content of this manuscript.

Informed consent

Informed consent was not required for the purpose of this study.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Luca Pasina
    • 1
  • Lorenzo Colzani
    • 2
  • Laura Cortesi
    • 1
  • Mauro Tettamanti
    • 1
  • Antonella Zambon
    • 2
  • Alessandro Nobili
    • 1
  • Andrea Mazzone
    • 3
  • Paolo Mazzola
    • 2
  • Giorgio Annoni
    • 2
    • 4
  • Giuseppe Bellelli
    • 2
    • 4
  1. 1.Istituto di Ricerche Farmacologiche Mario Negri IRCCSMilanoItaly
  2. 2.School of Medicine and SurgeryUniversity Milano-BicoccaMilanoItaly
  3. 3.Redaelli Geriatric InstituteMilanoItaly
  4. 4.Acute Geriatric UnitSan Gerardo HospitalMonzaItaly

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