We observed no difference in the anticholinergic burden of treatment at admission between delirium patients and the control group, despite the same prevalence of delirium as the other studies4. Our results confirmed previous studies16,24,27, while including a larger number of patients using scales based on comprehensive lists of anticholinergic drugs compared to other scales27.
These results can be explained by several factors. Firstly, the anticholinergic burden estimated by the scales used is low, which limits its effect on treatment as a predisposing factor for delirium, compared to other factors associated with delirium in multivariate analysis, such as male sex history of dementia, drug withdrawal and surgery, as already described2,5. Similarly, Passina et al. found that anticholinergic drugs increased the risk of delirium because of the cumulative effect, but this effect disappeared in the multivariate analysis after adjusting for dementia and malnutrition26.
We also believe that the anticholinergic load assessed by ADS, mADS and Marante Scale underestimates the overall treatment of our elderly impatients: indeed, our analysis was based on the patient's usual treatment on admission and did not take into account the possible anticholinergic load administered in hospital. We also observed that these scales do not assess the anticholinergic load in the same way: for example, the ADS only assesses the anticholinergic potency of the drugs, whereas the mADS and the MARANTE Scale combine the anticholinergic potency with the dose of the drug. Moreover, they do not necessarily consider the marketing of new drugs. For instance, MARANTE Scale lists only 41 drugs out of the 100 drugs in the Duran et al. reference list15. Finally, the number of patients taking anticholinergic drugs users was lower than that found in the study by Rigor et al., i.e., 49% versus 72.7%28.
Other studies have shown a positive association between delirium and anticholinergic burden22,26,29. This discrepancy may result from the great heterogeneity of the studies included in the literature reviews, whether due to the characteristics of the study (delirium is rarely the primary objective of the study), the study population (number of patients included, settings, age) or the scale used, the most commonly used scales being ACB and ADS16,24,26,28. According the litterature, only one study has analyzed modified ADS22 and two other have evaluated MARANTE scale14,30, which make it difficult to compare. In a recent study comparing 16 anticholinergic burden scales, Anticholinergic Cognitive load scale and ADS were considered to be the scales with the best inter-score agreement, with an inter-score correlation coefficient of 0.82. The performance of the scales varied according to the characteristics of the population studied. The main pitfall was a wide variation in the estimation of the average daily dose and anticholinergic potency of the drugs, which varied considerably from one list to another, as we have observed31. Two recent reviews have evaluated the association between anticholinergic burden and clinical course, showing divergent results, due to the type of scale, the type of patients and the retrospective or prospective nature of the studies included12,15.
In our study, none of the three scales was associated with length of stay, intra-hospital mortality, or one-year mortality. Only ADS and mADS scales in the control group were associated with intra-hospital mortality (respectively p = 0.029 and 0.049).
On the other hand, we have observed an association between anticholinergic burden according to ADS and mADS and female sex, which might be explained by the presence of drugs treating urinary incontinence that affects women more frequently.
Similarly, we observed an association between anticholinergic burden and living in nursing homes, which may be explained by a greater polypharmacy and an increased prescription of psychotropic drugs compared to people living at home, as described in the literature32
. The association of anticholinergic burden and depression could be explained by the fact that antidepressants and benzodiazepines are the most prevalent drugs in anticholinergic burden scales. However, we believe that the diagnosis of depression may have been overestimated as it is sometimes determined by the presence of an antidepressant in the intake treatment.
Our study presents some strengths.
The study took place in acute care medical and surgical services for comorbid and multi-medicated elderly people, representative of the frail geriatric population.
In addition, it included a large cohort over a five-years period, allowing for possible variations in medical conditions during hospitalization.
To our knowledge, this study is the first to compare the anticholinergic burden of two groups of older hospitalized patients with and without delirium according to three anticholinergic scales, including a scale validated on a Belgian population, the MARANTE Scale.
However, Marante Scale had a fairly good reliability with the ADS, which is more widely used in the literature. At least, it still needs to be studied on other populations and in other contexts. In addition, the modified version of the ADS did not add accuracy to detect a higher risk of delirium, which has not been described above.
The study has also some weaknesses. It is a single-center study, and methodologically limited
by its retrospective nature. This may explain why many factors associated with delirium could not be identified, including precipitating factors, limiting the interpretation of the lack of association between delirium and the anticholinergic burden.
Currently, anticholinergic scales are not yet standardized. They remain imprecise in drug categorization and do not consider inter-individual pharmacokinetic variability, as suggested by several systematic reviews33,34. Moreover, some scales such as ADS may have a "plateau" effect due to muscarinic receptor saturation or mode of action: Kersten et al. suggested that there is no increase in side effects when the anticholinergic burden is greater than 335.
In addition, a few studies have hypothesized that ADS would be a better predictor of peripheral anticholinergic effects (e.g., dry mouth, constipation) than central effects, such as delirium and cognitive decline16,34,35.