Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Association of Anticholinergic Drug Burden With Cognitive and Functional Decline Over Time in Dementia With Lewy Bodies: 1-Year Follow-Up Study.

BACKGROUND: The purpose of this study was to investigate the relationship between anticholinergic burden (ACB), and cognitive and functional alterations in patients with dementia of Lewy bodies (DLB) during a 1-year follow-up period. METHODS: This cohort study included patients diagnosed with DLB admitted to a tertiary geriatric outpatient clinic. Cognition, functional performance, and nutritional status were assessed at baseline, 6 months, and 12 months during the follow-up period. The ACB was evaluated, and participants were grouped as ACB ≥1 and ACB=0. RESULTS: A total of 112 patients with DLB (mean age, 79.3 ± 6.8 years; 50.9% female) were included. The mean number of medications was 5.1 ± 4, 56.9% of participants had polypharmacy, and 55.2% had an anticholinergic drug burden. Individuals with ACB ≥1 had lower instrumental activities of daily living (IADL) scores at baseline than those with ACB=0 (P=0.014). The Barthel index and Lawton-Brody IADL scores significantly decreased in the ACB ≥1 group on repetitive measurements over time, whereas only the Lawton-Brody IADL scores worsened in the ACB=0 group (all P<0.001). There were no significant differences in cognitive scores and Mini-Mental State Examination subdomains between the groups. The dependent variable repetitive test revealed a significant deterioration in the orientation subdomain in the ACB ≥1 group over time (P=0.001). Multivariable regression models showed no significant effect of ACB score on cognitive and functional impairment. CONCLUSION: Our study provides evidence that the use of anticholinergic drugs in this vulnerable population may potentially increase the morbidity by adversely affecting functional status and cognitive orientation.

An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that "extrapyramidal symptoms" is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually.

Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

OBJECTIVE: Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. MATERIALS AND METHODS: Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. RESULTS: Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). CONCLUSION: We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.

Association of pneumonia admission with polypharmacy and drug use in community-dwelling older people.

AIM: The purpose of the present study was to clarify the association of pneumonia admission with polypharmacy and specific drug use in community-dwelling older people. METHODS: Using health insurance and long-term care insurance data from Kure city in Japan, we retrospectively collected data for older community-dwelling people (aged ≥65 years) from April 2017 to March 2019. The outcome was pneumonia admission. We carried out multivariate logistic regression analysis to identify the association of pneumonia admission with polypharmacy (≥5 drugs), the use of psychotropic drugs or anticholinergics with adjustment for patient backgrounds, such as comorbidity, and the daily life independence level for the older people with disability. RESULTS: Of 59 040 older people, 4017 (6.8%) participants were admitted for pneumonia in 2 years. The ratio of polypharmacy, and the use of psychotropic drugs and anticholinergics in the admission group were significantly higher than the non-admission group. Multivariate logistic regression analysis showed that polypharmacy (odds ratio 1.29, 95% confidence interval 1.18-1.41), and the use of conventional antipsychotic drugs (odds ratio 1.39, 95% confidence interval 1.02-1.90), atypical antipsychotic drugs (odds ratio 1.67, 95% confidence interval 1.37-2.05) and anticholinergics (odds ratio 1.22, 95% confidence interval 1.13-1.33) were significantly associated with pneumonia admission. CONCLUSION: The present results suggest that polypharmacy, and the use of psychotropic drugs and anticholinergics are risk factors for pneumonia admission. Geriatr Gerontol Int 2024; 24: 404-409.

Investigating the association of anticholinergic burden with depression in older adults: a cross-sectional study.

BACKGROUND: Although depression and anticholinergic drug use are common comorbidities that impair health status in later life, there are insufficient data on their relationship. This study aimed to investigate the relationship between depressive symptoms and anticholinergic use in older individuals. METHODS: Community-dwelling older adults (≥65 years) admitted to the tertiary referral geriatric outpatient clinic were included. Participants were evaluated for depressive symptoms using the Geriatric Depression Scale (GDS) with a cut-off score of ≥6 for depression. Exposure to anticholinergic drugs was assessed using the anticholinergic cognitive burden (ACB) scale and three subgroups were created: ACB = 0, ACB = 1, and ACB ≥ 2. The relationship between these two parameters was assessed using multivariate logistic regression analysis considering other potential variables. RESULTS: The study included 1232 participants (mean age 78.4 ± 7.2 years and 65.2% female) and the prevalence of depression was 24%. After adjusting for potential confounders, compared to ACB = 0, having ACB ≥ 2 was related to depression symptoms (odds ratio (OR): 1.56, 95% CI: 1.04-2.35, P = 0.034), whereas having ACB = 1 did not increase the risk (OR: 1.27, 95% CI: 0.88-1.83, P = 0.205). CONCLUSION: Our findings indicate that special attention should be paid to drug therapy in preventing depression in older adults, as exposure to a high anticholinergic load is negatively associated with psychological status.

The impact of anticholinergic burden on clinical outcomes in older hospitalised surgical patients.

Polypharmacotherapy is an ever-increasing issue with an ageing patient population. Anticholinergic medications make up a large proportion of patient medication but cause significant side effects, contributing to well-documented issues within the older population and in hospital medicine. This review explores the documented impact of anticholinergic burden in older surgical patients on postoperative delirium, infection, length of stay and readmission, urinary retention, ileus and mortality. It also highlights the need for further high-quality research into anticholinergic burden management among older surgical patients to further impact practice and policy in the area.

The predictive value of anticholinergic drug exposure and the outcome of pneumonia: a Danish database study.

INTRODUCTION: Older adults are susceptible to anticholinergic effects. Dysphagia and pneumonia are associated with anticholinergic usage, though a definitive causative relationship has not been established. There is no effective way to predict the prognosis of older adults with pneumonia; therefore, this study investigates the predictive value of anticholinergic burden. METHODS: Patients aged 65 years and above admitted for community-acquired pneumonia from 2011 to 2018 in Denmark were included through Danish registries. We calculated anticholinergic drug exposure using the CRIDECO Anticholinergic Load Scale (CALS). The primary outcome was in-hospital mortality, and other outcomes included intensive care unit admission, ventilator usage, length of stay, 30-day/90-day/1-year mortality, institutionalisation, home care utilisation and readmission. RESULTS: 186,735 patients were included in the in-hospital outcome analyses, 165,181 in the readmission analysis, 150,791 in the institutionalisation analysis, and 95,197 and 73,461 patients in the home care analysis at follow-up. Higher CALS score was associated with higher in-hospital mortality, with a mean risk increasing from 9.9% (CALS 0) to 16.4% (CALS >10), though the risk plateaued above a CALS score of 8. A higher CALS score was also associated with greater mortality after discharge, more home health care, more institutionalizations and higher readmission rates. CONCLUSIONS: High anticholinergic burden levels were associated with poor patient outcomes including short-/long-term mortality, dependence and readmission. It may be useful to calculate the CALS score on admission of older patients with pneumonia to predict their prognosis. This also highlights the importance of avoiding the use of drugs with a high anticholinergic burden in older patients.

Association of systemic anticholinergic medication use and accelerated decrease in lung function in older adults.

Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.

Disentangling drug contributions: anticholinergic burden in older adults linked to individual medications: a cross-sectional population-based study.

BACKGROUND: Medications with potent anticholinergic properties have well-documented adverse effects. A high cumulative anticholinergic burden may arise from the concurrent use of multiple medications with weaker anticholinergic effects. We sought to identify patterns of high anticholinergic burden and associated patient characteristics. METHODS: We identified patients aged ≥ 65 who filled ≥ 1 medication with anticholinergic adverse effects in 2019 and had a cumulative Anticholinergic Burden score (ACB) ≥ 4 (i.e., high anticholinergic burden) in a large US health insurer. We classified patients based on how they attained high burden, as follows: 1) only filling strong or moderate anticholinergic medications (i.e., ACB = 2 or 3, "moderate/strong"), 2) only filling lightly anticholinergic medications (i.e., ACB = 1, "light/possible"), and 3) filling any combination ("mix"). We used multinomial logistic regression to assess the association between measured patient characteristics and membership in the three anticholinergic burden classifications, using the moderate/strong group as the referent. RESULTS: In total, 83,286 eligible patients with high anticholinergic burden were identified (mean age: 74.3 years (SD:7.1), 72.9% female). Of these, 4.5% filled only strong/moderate anticholinergics, 4.3% filled only light/possible anticholinergics, and the rest filled a mix (91.2%). Within patients in the mixed group, 64.3% of medication fills were for light/possible anticholinergics, while 35.7% were for moderate/strong anticholinergics. Compared with patients in the moderate/strong anticholinergics group, patients filling only light/possible anticholinergics were more likely to be older (adjusted Odds Ratio [aOR] per 1-unit of age: 1.06, 95%CI: 1.05-1.07), less likely to be female (aOR: 0.56, 95%CI: 0.50-0.62 vs. male), more likely to have comorbidities (e.g., heart failure aOR: 3.18, 95%CI: 2.70-3.74 or depression aOR: 1.20, 95%CI: 1.09-1.33 vs. no comorbidity), and visited fewer physicians (aOR per 1-unit of change: 0.98, 95%CI: 0.97-0.98). Patients in the mixed group were older (aOR per 1-unit of age: 1.02, 95%CI: 1.02-1.03) and less likely to be female (aOR: 0.89, 95%CI: 0.82-0.97 vs. male) compared with those filling moderate/strong anticholinergics. CONCLUSION: Most older adults accumulated high anticholinergic burden through a combination of light/possible and moderate/strong anticholinergics rather than moderate/strong anticholinergics, with light/possible anticholinergics being the major drivers of overall anticholinergic burden. These insights may inform interventions to improve prescribing in older adults.

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.

Changes in Anticholinergic Burden in Parkinson's Disease After Deep Brain Stimulation.

OBJECTIVE: This study aimed to evaluate the effect of deep brain stimulation (DBS) on anticholinergic burden in Parkinson's disease (PD) and the association of anticholinergic burden with cognition. MATERIALS AND METHODS: A retrospective chart review in patients with PD who underwent bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS from 2010 to 2020 reviewed medications with anticholinergic burden at baseline, six months, and one year (N = 216) after surgery. The cumulative anticholinergic burden at each visit was calculated using the Anticholinergic Risk Scale (ARS). RESULTS: ARS scores were significantly lower for patients six months and one year after surgery than at baseline (z = 6.58, p < 0.0001; z = 6.99, p < 0.0001). Change in ARS scores at both six months and one year were driven by down-titration of PD medications (z = 9.35, p < 0.0001; z = 8.61, p < 0.0001), rather than changes in pain, psychiatric, or urinary medications with anticholinergic effects. There was no significant difference in change in ARS scores at one year between targets (t = 0.41, p = 0.68). In addition, there was no significant association between anticholinergic burden and cognitive performance. CONCLUSION: GPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

OBJECTIVES: How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. METHODS: We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. RESULTS: We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78-0.92) and 0.84 (0.75-0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). CONCLUSIONS: Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population.

[Polypharmacy in patients with dementia]. / Polypharmazie bei Demenzerkrankten.

The number of patients with dementia is expected to grow in the coming years due to an aging population and an increasing life-expectancy. At the same time, in an aging society there will be an increase in multimorbidity and therefore polypharmacy. This combination presents numerous challenges particularly for people with dementia, as the correct administration of the drugs can frequently no longer be guaranteed. The drug treatment of neuropsychiatric symptoms of dementia are often treated with antipsychotics with potentially severe side effects and with limited efficacy. Moreover, many drugs have an anticholinergic potential, which may worsen the cognitive function even further in patients with dementia. The use of anticholinergic drugs should be handled with care and when possible be avoided in patients with dementia.

Association of the Drug Burden Index (DBI) exposure with outcomes: A systematic review.

BACKGROUND: The Drug Burden Index (DBI) measures an individual's total exposure to anticholinergic and sedative medications. This systematic review aimed to investigate the association of the DBI with clinical and prescribing outcomes in observational pharmaco-epidemiological studies, and the effect of DBI exposure on functional outcomes in pre-clinical models. METHODS: A systematic search of nine electronic databases, citation indexes and gray literature was performed (April 1, 2007-December 31, 2022). Studies that reported primary data on the association of the DBI with clinical or prescribing outcomes conducted in any setting in humans aged ≥18 years or animals were included. Quality assessment was performed using the Joanna Briggs Institute critical appraisal tools and the Systematic Review Centre for Laboratory animal Experimentation risk of bias tool. RESULTS: Of 2382 studies screened, 70 met the inclusion criteria (65 in humans, five in animals). In humans, outcomes reported included function (n = 56), cognition (n = 20), falls (n = 14), frailty (n = 7), mortality (n = 9), quality of life (n = 8), hospitalization (n = 7), length of stay (n = 5), readmission (n = 1), other clinical outcomes (n = 15) and prescribing outcomes (n = 2). A higher DBI was significantly associated with increased falls (11/14, 71%), poorer function (31/56, 55%), and cognition (11/20, 55%) related outcomes. Narrative synthesis was used due to significant heterogeneity in the study population, setting, study type, definition of DBI, and outcome measures. Results could not be pooled due to heterogeneity. In animals, outcomes reported included function (n = 18), frailty (n = 2), and mortality (n = 1). In pre-clinical studies, a higher DBI caused poorer function and frailty. CONCLUSIONS: A higher DBI may be associated with an increased risk of falls and decreased function and cognition. Higher DBI was inconsistently associated with increased mortality, length of stay, frailty, hospitalization or reduced quality of life. Human observational findings with respect to functional outcomes are supported by preclinical interventional studies. The DBI may be used as a tool to identify older adults at higher risk of harm.

The effect of the anticholinergic burden on mortality following elective cardiac surgery.

OBJECTIVE: The cumulative effect of drugs with anticholinergic properties may pose a significant risk in the post-discharge period of patients who have undergone elective cardiac surgery. The aim of this study was to investigate the association between anticholinergic burden and 6-month postdischarge mortality in older cardiac surgery patients. METHODS: This study performed a retrospective longitudinal analysis of patients undergoing elective cardiac surgery at a tertiary care centre from January 2021 to January 2022. The Deyo-Charlson comorbidity index (D-CCI) was used to estimate the burden of comorbidities. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale (ACB) and Drug Burden Index (DBI) scale. All-cause postdischarge mortality was determined from electronic medical records. RESULTS: A total of 255 older adults who had undergone elective cardiac surgery and had been followed up for at least 6 months were included in this study. Approximately 12.5% (n = 32) of older patients died within 6 months of discharge. In multivariate Cox regression analysis, ACB (HR:1.31, 95%CI:1.10-1.56 p = 0.01) and DBI (HR:2.08, 95%CI:1.27-3.39 p = 0.01) showed significantly increased risk of 6-month postdischarge mortality after adjusting for several possible confounders (age, gender, D-CCl, and American Society of Anaesthesiologists (ASA) score). Overall event-free survival differed significantly between patients undergoing cardiac surgery based on anticholinergic burden according to the group-stratified ACB and DBI scales (χ2: 5.907, log-rank test, p = 0.015 and χ2: 15.389, log-rank test, p < 0.001 respectively). CONCLUSION: The anticholinergic burden is associated with 6-month all-cause post-discharge mortality in older cardiac surgery patients. A deprescribing approach should be considered, especially for older adults in the perioperative period. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov. Identifier: NCT05312684 Registered on 5 April 2022.

Pharmcokinetic and pharmacodynamic considerations for the anticholinergic burden scale of drugs.

Older adults frequently have many systemic diseases that require treatment with multiple drugs, and thus anticholinergic adverse effect by polypharmacy is a significant concern in the management of older adults. The accuracy of the anticholinergic burden rating may be increased by considering pharmacokinetic and pharmacodynamic factors such as biophase drug concentrations, the pharmacologically active metabolites formed after drug administration, and muscarinic receptor-mediated effects. Therefore, a pharmacological evidence-based burden scale that considers pharmacokinetic and pharmacodynamic factors is expected to be a more optimal tool for precisely assessing the anticholinergic burden, specifically risk reductions in anticholinergic adverse events in the poly-medicated elderly. Geriatr Gerontol Int 2024; 24: 81-87.

Increased anticholinergic medication use in middle-aged and older autistic adults and its associations with self-reported memory difficulties and cognitive decline.

Many commonly used prescription and over-the-counter medicines have potent anticholinergic (AC) effects. Among older adults, AC medications are associated with cognitive impairment and risk for cognitive disorders, including Alzheimer's disease. Collectively, the impact of AC medications is known as anticholinergic cognitive burden (ACB). Because of the high rates of co-occurring medical and psychiatric conditions, autistic adults may have high AC exposure and, thus, may experience elevated ACB. However, no research has characterized AC exposure or examined its associations with cognitive outcomes in autistic adults. Autistic adults (40-83 years) recruited via Simons Powering Autism Research's (SPARK) Research Match service self-reported their medication use (N = 415) and memory complaints (N = 382) at Time (T)1. At T2, 2 years later, a subset of T1 participants (N = 197) self-reported on decline in cognition. Medications were coded using two scales of AC potency. A high proportion (48.2%-62.9%, depending upon the AC potency scale) of autistic adults reported taking at least one medication with AC effects, and 20.5% to 26.5% of autistic adults reported clinically-relevant levels of AC medication (potency ≥3). After controlling for birth-sex, and age, hierarchical linear regression models showed total ACB scores and AC potency values of ≥3 predicted greater memory complaints. Logistic regression models showed that AC medicines at T1 were associated with self-reported cognitive decline at follow-up 2 years later. Understanding AC medications-including potentially earlier AC polypharmacy-and their impacts on cognition (e.g., dementia risk) in autistic adults is warranted.

Gender-specific linkages: frailty, polypharmacy, anti-cholinergic burden, and 5-year mortality risk-a real-world analysis.

Background: With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. More importantly, the properties of anti-cholinergic drugs contribute various negative effects. This study aimed to investigate the sex difference in the association of polypharmacy, anticholinergic burden, and frailty with mortality. Methods: Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment data were collected and the phenotype of frailty was determined by Fried's criteria. Cox regression and the Kaplan-Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks. Results: Of the 2,077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score, and greater anticholinergic burden were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. In frail female group, individuals with a higher anticholinergic burden (as indicated by the Anticholinergic Cognitive Burden Scale) from drug usage exhibited an elevated 5-year mortality rate. Conclusions: Polypharmacy and greater anticholinergic burden, synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy and anticholinergic burden in the older population.

Anticholinergic burden of medications is associated with dry mouth and reflected in minor labial gland secretion.

OBJECTIVE: Medications with anticholinergic potential inhibit saliva secretion. Polypharmacy potentiates anticholinergic burden, causing dry mouth symptoms and chronic deterioration of oral health. Patients of any age can be affected by anticholinergic medication-triggered hyposalivation (the objective measure of dry mouth); therefore, seeking predictions of hyposalivation to screen dry mouth is needed. DESIGN: In our prospective, cross-sectional clinical study, 55 middle-aged adult patients participated. We examined whether the anticholinergic burden calculated from anticholinergic medications (anticholinergic drug score; ADS) and blood serum anticholinergic activity (SAA; the gold standard measure of anticholinergic burden) is associated with hyposalivation. As no prior studies measured minor salivary glands regarding the quantifiable anticholinergic burden, we assessed hyposalivation by the minor saliva flow (MSF) and unstimulated whole saliva (UWS) secretion. RESULTS: Our data showed a negative linear relationship between SAA and UWS (p < 0.05); when SAA increases by one pmol/ml unit, the saliva flow decreases by 0.058 ml/min. MSF showed a linear correlation (p < 0.005) with UWS. In a multivariate logistic regression model (including age, gender, race, smoking status, xerostomia severity, ADS, and BMI), we identified SAA and age as predictors of hyposalivation (p < 0.05). CONCLUSIONS: We provide evidence for the significant relationship between measurable anticholinergic burden and saliva flow. The correlation between UWS and MSF suggests that both saliva flow rate measurement methods could reflect anticholinergics-induced changes in salivary health.