Association Between Pneumonia Risk and Anticholinergic Burden Among Patients with Different Frailty Levels

Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor. Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre-existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation. We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science. We included prospective and retrospective longitudinal cohort and case-control observational studies, with a minimum of one-month follow-up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre-existing diagnoses of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random-effects meta-analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. MAIN RESULTS: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk ofgreater long-term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low- or very low-certainty evidence for all outcomes. AUTHORS' CONCLUSIONS: There is low-certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation.

Drugs with anticholinergic effects are associated with adverse events such as delirium and falls as well as cognitive decline and loss of independence. The aim of the study was to evaluate the association between anticholinergic burden and both cognitive and functional status, according to the hypothesis that the cumulative anticholinergic burden, as measured by the Anticholinergic Cognitive Burden (ACB) Scale and Anticholinergic Risk Scale (ARS), increases the risk of cognitive decline and impairs activities of daily living. This cross-sectional, prospective study (3-month telephone follow-up) was conducted in 66 Italian internal medicine and geriatric wards participating in the Registry of Polytherapies SIMI (Società Italiana di Medicina Interna) (REPOSI) study during 2010. The sample included 1,380 inpatients aged 65 years or older. Cognitive status was rated with the Short Blessed Test (SBT) and physical function with the Barthel Index. Each patient's anticholinergic burden was evaluated using the ACB and ARS scores. The mean SBT score for patients treated with anticholinergic drugs was higher than that for patients receiving no anticholinergic medications as also indicated by the ACB scale, even after adjustment for age, sex, education, stroke and transient ischaemic attack [9.2 (95 % CI 8.6-9.9) vs. 8.5 (95 % CI 7.8-9.2); p = 0.05]. There was a dose-response relationship between total ACB score and cognitive impairment. Patients identified by the ARS had more severe cognitive and physical impairment than patients identified by the ACB scale, and the dose-response relationship between this score and ability to perform activities of daily living was clear. No correlation was found with length of hospital stay. Drugs with anticholinergic properties identified by the ACB scale and ARS are associated with worse cognitive and functional performance in elderly patients. The ACB scale might permit a rapid identification of drugs potentially associated with cognitive impairment in a dose-response pattern, but the ARS is better at rating activities of daily living.

Medications with anticholinergic effects are commonly used in nursing homes, and their cumulative effect is of particular concern for the risk of adverse effects on cognition. The relation between cognitive function and anticholinergic burden measured with four scales, the Anticholinergic Cognitive Burden (ACB) Scale, the Anticholinergic Risk Scale, the German Anticholinergic Burden Scale, and the CRIDECO Anticholinergic Load Scale, is assessed according to the hypothesis that a higher anticholinergic burden is associated with reduced cognitive performance. This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term-care nursing homes (NH). Sociodemographic details, diagnosis, and drug treatments of each NH resident were collected using medical records four times during 2018 and 2019. Cognitive status was rated with the Mini-Mental State Examination (MMSE). The prevalence of anticholinergic use and its burden were calculated referring to the last time point for each patient. A longitudinal analysis was done on NH residents with at least two MMSE between 2018 and 2019 to assess the relation between the anticholinergic load and decline in MMSE. The relationship between drug-related anticholinergic burden and cognitive performance was analyzed using Poisson regression model theory. Multivariate analyses were adjusted according to the known risk factors of reduced cognitive performance available [age, sex, history of stroke or transient ischemic attack (TIA), and number of non-anticholinergic drugs] and for cholinesterase inhibitors. In view of the high number of subjects with an MMSE score = 0 among residents with dementia, for this group a zero-inflated Poisson regression model was used to give more consistent results. The association of anticholinergic burden with mortality was examined from each patient's last visit using a multivariate logistic model adjusted for age, sex, and Charlson Comorbidity Index (CCI). Among 1412 residents recruited, a clear direct relationship was found between higher anticholinergic burden and cognitive impairment only for the Anticholinergic Cognitive Burden Scale. Residents taking an anticholinergic who scored 5 or more had 2.5 points more decline than those not taking them (p < 0.001). Among residents without dementia there was a trend toward direct relationship for the Anticholinergic Cognitive Burden Scale and the Anticholinergic Risk Scale. Residents with higher scores had about 2 points more decline than residents not taking anticholinergic drugs. No relation was found between anticholinergic burden and cognitive decline or mortality. The cumulative effect of medications with modest antimuscarinic activity may influence the cognitive performance of NH residents. The anticholinergic burden measured with the ACB scale should help identify NH residents who may benefit from reducing the anticholinergic burden. A clear direct relationship between anticholinergic burden and cognitive impairment was found only for the ACB Scale.

ObjectiveTo evaluate the association between recently raised anticholinergic burden and risk of acute cardiovascular events in older adults.DesignCase-case-time-control study (ie, incorporating a case crossover design and a control crossover design...

Actuality . The pharmacotherapy practice in elderly and senile patients is characterized by a widespread use of drugs with anticholinergic properties. Available data indicate that the combined anticholinergic cognitive burden correlates with the risk of adverse events and may serve as a factor in increasing the frequency of hospitalization in elderly patients. Objective. To examine the prevalence of anticholinergic medications and factors associated with anticholinergic cognitive burden in this study population. Methods. A retrospective pharmacoepidemiological analysis of medical records of 401 patients >65 years of age, hospitalized in Moscow in the period from 1st of June to 30th of December, 2017, was performed. Anticholinergic drugs were identified using Anticholinergic Cognitive Burden Scale (ACB) [Anticholinergic cognitive burden scale. Aging Brain Care. 2012 Update Developed by the Aging Brain Program of the Indiana University Center for Aging Research]. Binary logistic regression was applied to identify significantly the factors associated with anticholinergic medication use in the study population. Data were presented using odds ratios with 95 % confidence intervals. Results. Four hundred one patients were included in the analysis, with a mean age of 77.4 (±7.2) years, 72.1 % were female, the median (IQR) of comorbidities per patient was 3 (0-5), the median of the number of prescribed medications per patient was 2 (0-4). The most common pathological conditions included chronic heart failure, hypertension, cerebrovascular disease, coronary heart disease. Polypharmacy was observed in 36.7% of patients. according to the ACB scale, 41.9 % of patients were exposed to ACB-contributing medicines (95 % CI: 41.1-42.7). Mean ACB score was 0.71 ± 0.06 (IQR 1-7). The most commonly prescribed ACB- contributing medications were cardiovascular agents — 51.47 %; and oral anticoagulants — 23.4 %. The odds of ACB exposure was 1.47 (CI 95 % = 1.33-1.63). The prescription of drugs with anticholinergic burden was not associated with an increase in the frequency of hospitalization (OR: 0.83, p = 0.089). Patients with ACB>0 had higher levels of potentially inappropriate medications (PIMs) (OR: 1.29, p = 0.02). An association of polypharmacy with high ACB scores was found (p = 0.001). No association was observed between potentially prescribing omission (PPOs), age and gender with Anticholinergic burden (ACB). Conclusions. Pharmacotherapy analysis of elderly and senile patients showed high prevalence rates of prescribing drugs with potential anticholinergic effects of level 1 according to ACB scale). There was no association between prescribing anticholinergics with an increased risk of hospitalization and the number of concomitant diseases.

Introduction Polypharmacy and anticholinergic burden are associated with falls in older people. A longitudinal study found patients with five or more drugs had 21% increased falls over 2 years. [Dhalwani, Fahami, Sathanapally et al, BMJ Open, 2017,7(10), e016358]. A cohort study identified a 1.51 odds of recurrent falls with anticholinergic medication, while taking multiple anticholinergics resulted in 100% likelihood of recurrent falls. [Marcum, Wirtz, Pettinger, et al, BMC Geriatrics, 2016,16,76]. Methods Retrospective study of polypharmacy in older people in Brunei based on data from Bru-HIMS, the Brunei public healthcare sector electronic prescribing and pharmacy management system. In this national study, stratified sampling was done by district, with patients randomly selected within each district. Active medications were identified from Bru-HIMS. The Anticholinergic Cognitive Burden (ACB) Scale was used to calculate anticholinergic burden. Findings for two districts (Tutong and Temburong) are described. Results For the 327 patients, 142 (43%) were male and 185 (57%) female. Median age was 72 years (Range 65 to 103 years). 234 (72%) had 5 drugs or more prescribed. Of the 2332 prescriptions, 268 (11.5%) had anticholinergic activity on the ACB scale. Median ACB score was 1. The most commonly prescribed were Orphenadrine, Chlorpheniramine, Diphenhydramine, Cinnarizine and Amitriptyline. There was a positive correlation between polypharmacy and anticholinergic burden (r = 0.4593). Conclusion There was a high rate of polypharmacy in older people, with anticholinergic drug burden identified. It may be useful to educate clinicians and patients regarding risks of polypharmacy and anticholinergic burden, including falls.

Anticholinergic burden is associated with recurrent and injurious falls in older individuals

Introduction Anticholinergic medications are commonly prescribed to older patients, particularly nursing home patients. Anticholinergic burden caused by these medications increases the risk of cognitive impairment, falls, delirium and increased mortality in this patient cohort. There are several published tools available to assess the impact of anticholinergic burden on patient negative outcomes (e.g. falls, cognitive impairment, hospitalisation, mortality). The Anticholinergic Cognitive Burden (ACB) scale is a validated tool which calculates a patient’s total anticholinergic medication score, to allow an estimation of cognitive burden (1). Aim The aim of this study was to describe the anticholinergic cognitive burden of medications in a cohort of nursing home patients using the ACB scale. Methods An observational study was conducted which involved screening patients’ pharmacy dispensing records for three nursing homes. All nursing homes which the pharmacy provides services for were sent an information leaflet and invited to participate, three agreed, with Directors of Nursing and General Practitioners providing consent. Medications contributing to Anticholinergic cognitive burden were recorded in Microsoft Excel by the researcher and patients total ACB score was calculated (1). A sample of 20% of patient scores was independently checked by another researcher for accuracy. Patients’ comorbidity data and cognitive function measure (Mini Mental State Examination or Mental Test Score) was recorded from their nursing home records by the researcher. Long-term nursing home patients ≥65-years-old were eligible for inclusion. Descriptive analysis was conducted. Results In total, the medications of 254 patients were assessed using the ACB score (63.4% female, mean age 83.5 ±7.79 -years-old). Of these, 195/254 (76.8%) were prescribed at least one anticholinergic medication. There were 132/254 (51.9%) patients with a total ACB score of ≥3 which is clinically significant and increases the risk of negative outcomes. The three most commonly prescribed anticholinergics were quetiapine (82/254, 32.3%), olanzapine (32/254, 12.6%) and furosemide (31/254, 12.2%). Of the patients with an ACB score ≥3, 58/132 (49.9%) had dementia and 63/132 had hypertension (47.7%). Conclusion This study highlights the high prevalence of anticholinergic medication prescribing in an Irish nursing home population. This is high in comparison with other European and international studies where lower ACB scores in nursing home populations have been recorded (2). The study was limited as it was only conducted in three nursing homes, a larger study may identify different prescribing patterns and ACB scores. Further work in pharmacy practice to include the ACB score as part of patients’ medication reviews is recommended. Collaboration with nursing home prescribers and nurses to increase awareness of anticholinergic medication risks and review is vital. Reductions in ACB scores would reduce the risk of falls, cognitive impairment and harm to these patients.

Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown. Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by -0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for. Anticholinergic burden has a significant impact on patients' ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.

A Preliminary Study of Anticholinergic Burden and Relationship to a Quality of Life Indicator, Engagement in Activities, in Nursing Home Residents With Dementia

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.

Older adults with dementia are particularly vulnerable to adverse outcomes resulting from anticholinergic use. We aimed to: (i) Examine the anticholinergic burden of patients with dementia attending a Psychiatry of Later Life (PLL) service (ii) Examine concomitant prescription of acetylcholinesterase inhibitors (AChEIs) and anticholinergics and (iii) Compare the Anticholinergic Cognitive Burden (ACB) scale with a recently published composite list of anticholinergics. Retrospective chart review of new referrals with a diagnosis of dementia (n = 66) seen by the PLL service, Tallaght University Hospital, Dublin, Ireland, over a consecutive period of 4 months. The mean ACB score was 2.2 (range = 0-9, SD = 2.1). 37.9% (n = 25) had a clinically significant ACB score (>3) and 42.1% (n = 8) of those taking AChEIs had a clinically significant ACB score. A significantly greater number of medications with anticholinergic activity were identified using the composite list versus the traditional ACB scale (2.3 v.1.5, p = 0.001). We demonstrated a significant anticholinergic burden amongst patients with dementia attending a specialist PLL service. There was no difference in anticholinergic burden between groups prescribed and not prescribed AChEIs, indicating that these medications are being prescribed without discontinuation of potentially inappropriate medications with anticholinergic activity. The true anticholinergic burden experienced by patients may be underestimated by the use of the ACB score alone, although the clinical significance of this finding is unclear. Calculation of true clinical anticholinergic burden load and its translation to a specific rating scale remains a challenge.

This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales. Experimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood-brain barrier penetration, bioavailability, chemical structure and P-glycoprotein (P-gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10-fold cross-validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity. In silico software (ADMET Predictor) used for screening drugs for their blood-brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25). Our findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability.

Objectives: The study aimed to investigate the association of anticholinergic burden with polypharmacy, the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the modified Hoehn and Yahr (HY) staging system in Parkinson's disease (PD). Patients and methods: The cross-sectional study included 75 patients (38 males, 37 females; mean age: 65.7±9.6 years; range, 32 to 86 years) who were admitted between January 2023 and January 2024. Demographic characteristics, systemic diseases, medications, MDS-UPDRS, and modified HY were recorded. Polypharmacy was defined as the use of five or more medications at the same time. The anticholinergic burden was calculated using the Anticholinergic Cognitive Burden (ACB) scale. Patients were divided into two groups: those with an ACB risk score ≥3 (high risk) and those with a risk score &lt;3 (low risk). Results: When analyzed according to ACB scale risk status, 41 patients with PD were found to be at high risk for anticholinergic burden (score ≥3). The presence of at least one comorbid disease was more common in the high-risk group than in the low-risk group (p&lt;0.05). The presence of unipolar depression was higher in the high-risk group (p=0.001). Frequency of polypharmacy was higher in the high-risk group (73.2% vs. 32.4%; p=0.001). In regression analysis, a high ACB score was statistically associated with modified HY Stage 4 when confounding factors were excluded (odds ratio=12.80; p=0.030). Conclusion: Patients with polypharmacy in PD had higher ACB scores (&gt;3) and depression as a comorbidity in these patients. A high ACB risk score was associated with modified HY Stage 4 when adjusted for confounding factors. The anticholinergic risk might be highest in the advanced stage of PD. Therefore, patients diagnosed with PD should be questioned about their drug history and evaluated for anticholinergic drug use at every visit.

Introduction: Anticholinergic burden may be an important risk factor for the cognitive impairment. Especially in polypharmacy, even drugs with low anticholinergic effects may contribute to a significant anticholinergic burden. The drugs with anticholinergic effects are used in treatment of motor and nonmotor symptoms of Parkinson’s disease (PD). Therefore, it is important to screen for polypharmacy and anticholinergic burden in PD patients with mild cognitive impairment (MCI). Methods: This cross-sectional study was conducted with 58 patients with PD. PD-MCI was diagnosed according to MDS Level 2 Comprehensive Assessment. Cognitive performance (attention – working memory, executive functions, language, memory, and visuospatial functions) of patients was evaluated. The anticholinergic burden was scored by Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), and Anticholinergic Drug Scale (ADS). Results: There was no significant difference in anticholinergic burden between PD-MCI and PD-normal cognition. A significant concordance was observed between ACB, ARS, and ADS scores (p < 0.001; Kendall’s W = 0.653). While the variable predicting anticholinergic burden was the total number of drugs for ACB and ADS scales, it was the number of antiparkinson drugs for ARS scale. Conclusion: Patients with PD are at high risk for polypharmacy and anticholinergic burden. Anticholinergic burden should be considered in the selection of drugs, especially for comorbidities in patients with PD. No significant correlation was found between the cognition and anticholinergic burden in patients with PD-MCI. Although the risk scores of antiparkinson and other drugs were different among the 3 scales, significant concordance was observed between scales.