Comparison of Anticholinergic Burden Scales and Their Association with Cognitive and Functional Impairment in Older Adults: A Cross-Sectional Study Using the REPOSI Database
- PMID: 40234370
- DOI: 10.1007/s40266-025-01204-6
Comparison of Anticholinergic Burden Scales and Their Association with Cognitive and Functional Impairment in Older Adults: A Cross-Sectional Study Using the REPOSI Database
Abstract
Background: The increasing use of anticholinergic medications in older adults with multiple chronic conditions raises significant concerns regarding their cumulative anticholinergic burden, which is linked to several adverse outcomes. This study aimed to compare existing anticholinergic burden scales to identify those most effective at correlating drug-induced anticholinergic load with cognitive and functional impairment. In addition, we proposed a new classification system on the basis of published scales to optimally correlate total anticholinergic burden with observed clinical deficits.
Methods: This cross-sectional study analyzed data from the REPOSI registry, which collects clinical and therapeutic information on patients aged 65 years and older admitted to internal medicine and geriatric wards across Italy. Anticholinergic exposure was assessed using 20 established anticholinergic burden scales from literature. In addition, seven experimental scales were developed on the basis of published scales and various mathematical functions (maximum, mode, median, and mean) to evaluate potential differences in measuring anticholinergic load. Outcomes included cognitive impairment, assessed using the Short Blessed Test (SBT), and functional independence, measured by the Barthel Index (BI). A zero-inflated negative binomial model was applied to analyze associations between anticholinergic burden and each outcome. Given the variability in drug scoring across published scales, we developed seven experimental scales using different mathematical functions (maximum, mode, median, and mean) to standardize scoring. Three versions included a null-score adjustment to account for drugs omitted in some scales, ensuring a more comprehensive measure of anticholinergic burden.
Results: Among 7735 patients, higher anticholinergic burden was consistently associated with increased cognitive impairment (SBT) and physical dependency (BI) across all existing and proposed scales. The modified Anticholinergic Risk Scale (mARS) scale showed the strongest associations with cognitive (rate ratio [RR] 1.10, 95% confidence interval [CI] 1.06, 1.13; P < 0.0001) and physical impairment (RR 1.18, 95% CI 1.11, 1.24; P < 0.0001), indicating an 18% higher risk of dependency per unit increase, while the CRIDECO Anticholinergic Load Scale (CALS) scale exhibited the best model fit. Our newly developed scales confirmed these associations, with the median with null score and the mean with null score scale showing the strongest link to cognitive impairment (RR 1.07, 95% CI 1.05, 1.09; P < 0.0001) and the strongest association with physical dependency (RR 1.11, 95% CI 1.08, 1.15; P < 0.0001).
Conclusions: Scales that identify a greater proportion of patients with at least one anticholinergic drug may provide a more comprehensive assessment of anticholinergic burden in clinical practice. While no single scale demonstrated a definitive advantage across all outcomes, these scales may identify patients at risk. Prioritizing the use of scales with broader coverage could enhance clinical decision-making and optimize management of polypharmacy in older adults and recognize its potential impact on cognitive and functional outcomes.
© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Conflict of interest statement
Declarations. Funding: No sources of funding were used in the conduct of this study or the preparation of this article. Conflict of interest: The authors have no conflicts of interest that are directly relevant to the content of this article. Ethical approval: The study protocol was approved by the ethics committee of the coordinating center and then ratified by the local committee of all participating hospitals. Consent to participate: This was a retrospective study and data collection complied fully with Italian law on personal data protection. All data were anonymous, and informed consent was not required for the purpose of the study. Consent for publication: Not applicable. Data availability statement: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Code availability: The codes that support the findings of this study are available on request from the corresponding author. Author contributions: All authors participated in drafting or critical revision for important intellectual content. Individual contributions are as follows: M.A. and L.P. designed the study, interpreted data, and wrote the manuscript; A.N. performed and interpreted statistical analyses; L.P. carried out the final critical revision for important intellectual content. All authors read and approved the final version of the paper and agree to be accountable for the work. All authors had full access to all data and take responsibility for its integrity and the accuracy of the data analysis (see Electronic Supplementary Material S1 for a list of investigators and co-authors of the REPOSI Study Group).
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