Anticholinergic Research Articles

Deprescribing as a Way to Reduce Inappropriate Use of Drugs for Overactive Bladder in Primary Care (DROP): Protocol for a Cluster Randomized Controlled Trial With an Embedded Explanatory Sequential Mixed Methods Study.

Potentially inappropriate medication remains a significant concern in general practices, particularly in the context of overactive bladder (OAB) treatment for individuals aged 65 years and older. This study focuses on the exploration of alternative options for treating OAB and the deprescribing of anticholinergic drugs commonly used in OAB. The research aims to comprehensively evaluate the efficiency of deprescribing through a mixed methods approach, combining quantitative assessment and qualitative exploration of perceptions, experiences, and potential barriers among patients and health care personnel. This study aims to evaluate the efficiency and safety of the intervention in which health care staff in primary care encourage patients to participate in deprescribing their drugs for OAB. In addition, we aim to identify factors contributing to or obstructing the deprescribing process that will drive more informed decisions in the field of deprescribing and support effective and safe treatment of patients. The drugs for overactive bladder in primary care (DROP) study uses a rigorous research design, using a randomized controlled trial (RCT) with an embedded sequential explanatory mixed methods approach. All general practices within the North Denmark Region will be paired based on the number of general practitioners (GPs) and urban or rural locations. The matched pairs will be randomized into intervention and control groups. The intervention group will receive an algorithm designed to guide the deprescribing of drugs for OAB, promoting appropriate medication use. Quantitative data will be collected from the RCT including data from Danish registries for prescription analysis. Qualitative data will be obtained through interviews and focus groups with GPs, staff members, and patients. Finally, the quantitative and qualitative findings are merged to understand deprescribing for OAB comprehensively. This integrated approach enhances insights and supports future intervention improvement. The DROP study is currently in progress, with randomization of general practices underway. While they have not been invited to participate yet, they will be. The inclusion of GP practices is scheduled from December 2023 to April 2024. The follow-up period for each patient is 6 months. Results will be analyzed through an intention-to-treat analysis for the RCT and a thematic analysis for the qualitative component. Quantitative outcomes will focus on changes in prescriptions and symptoms, while the qualitative analysis will explore experiences and perceptions. The DROP study aims to provide an evidence-based intervention in primary care that ensures the deprescription of drugs for OAB when there is an unfavorable risk-benefit profile. The DROP study's contribution lies in generating evidence for deprescribing practices and influencing best practices in health care. ClinicalTrials.gov NCT06110975; https://clinicaltrials.gov/study/NCT06110975. DERR1-10.2196/56277.

Case report on Ipratropium Bromide induced Anisocoria

Anisocoria or unequal pupil size is an alarming sign of a neurologic emergency, especially when the patient is in a critical care setting. It is important to identify the aetiology of anisocoria and consider drug-induced anisocoria as a possible aetiology after ruling out underlying pathology if any. Ipratropium bromide, an anticholinergic drug, can cause anisocoria. This case report emphasises Ipratropium bromide-induced anisocoria.

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

BackgroundMedications 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.MethodsWe 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.ResultsIn 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.ConclusionMost 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.

Risk of dementia among antidepressant elderly users: A population-based cohort analysis in Spain

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624–2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818–2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance.Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed.

Provider-reported use of butylscopolamine in gastrointestinal endoscopy in Germany.

Introduction The anti-cholinergic agent hyoscine-N-butylbromide (HBB) is used in gastrointestinal (GI) endoscopy to decrease motility and facilitate endoscopic procedures. Data from clinical studies to support this practice is limited especially for therapeutic procedures. Likewise, patterns of use among endoscopist are largely unclear. This study sought to assess usage of HBB among German-speaking endoscopists. Material and Methods We conducted an anonymous online survey among endoscopists in German-speaking countries. Results A total of 207 physicians participated in the survey. The majority (76.9%) were experienced endoscopists and 92.3% of respondents use HBB at least occasionally during procedures. The reported median stated frequency of HBB use varied greatly between different types of procedures and increased with the complexity of the procedure being performed. HBB was rarely used in diagnostic esophagogastroduodenoscopies (EGD) (median stated frequency 1% of procedures), while use frequency was significantly higher in EGD with endoscopic mucosal resection (EMR) (10%; p=0.002) and EGD with endoscopic submucosal dissection (ESD) (20%; p<0.001). Similarly, use frequency during diagnostic colonoscopy was lower (5%) compared to colonoscopy with EMR (20%, p=0.005) or ESD (42.5%, p<0.001). The highest use frequency was reported for ERCP (50%). The most frequently stated reason to use HBB was facilitation of the procedure (80.6%) followed by increasing diagnostic yield (58.3%). Conclusion German-speaking endoscopists commonly use HBB, most frequently to facilitate complex therapeutic procedures. Given there is almost no data supporting HBB use in therapeutic endoscopy, we suggest that more research is needed to evaluate benefits and risks of this practice.

Эффективность и безопасность комбинированной терапии препаратами алфузозин (Алфупрост® МР) и солифенацин (Везигамп) у больных доброкачественной гиперплазией предстательной железы и гиперактивным мочевым пузырем: первые результаты наблюдательного многоцентрового исследования «АВИАТОР».

Introduction. Combination therapy of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) with the use of α1-adrenoblockers and anticholinergic drugs has become the standard of treatment and is widely used in clinical practice. Materials and methods. An observational prospective multicenter study was conducted to evaluate the efficacy and safety of combined alfuzosin (Alfuprost ® MR) 10 mg/day and solifenacin (Vesigamp) 5 mg/day in patients with BPH and overactive bladder (OAB) with moderate and severe symptoms in real outpatient practice. The study included 208 patients with LUTS/BPH 60.7±6.4 years old with the following average indicators: international prostate symptom score (IPSS) – 20.2±4.9 points; obstructive symptoms – 10.8±4.2 and irritative symptoms – 9.4±2.1 (nocturia 2.8±1.0); quality of life (QoL) - 4.8±0.5; the prostate volume is 49.9±12.0 cm3 ; intravesical prostatic protrusion &lt; 10 mm; overactive bladder symptom score (OABSS) – 10.5±2.4; patient perception of intensity of urgency scale (PPIUS) – 2.5±0.7; maximum flow rate (Qmax) – 11.5±2.1 ml/s; average flow rate (Qave) – 6.6±1.5 ml/s; urinary volume (Vcomp) – 204.1±51.4 ml; residual urine (Vres) – 49.7±35.3 ml. Control examinations were performed 1 and 3 months after the start of treatment. Results. The overwhelming number of patients achieved a statistically reliable and pronounced effect on most subjective and objective clinical indicators, which was registered a month after the start of combination treatment and intensified by the third month of follow-up. A significant improvement in LUTS according to IPSS was after 1 and 3 months, respectively: total score -45.5% and -72.3%; irritative symptoms -45.7% and -73.4%; obstructive -45.4% and -72.2%; nocturia -46.4% and -71.4%; QoL -50.0% and -79.1%. A statistically significant decrease in OAB symptoms according to the OABSS questionnaire was -50.5% and -80.9% after 1 and 3 months, respectively, including imperative urinary incontinence -50.0% and -83.3%. There was also a significant decrease in the severity of urgency according to the PPIUS questionnaire: by -52.0% and -88.0%. Combination therapy led to a rapid and significant improvement in the objective parameters of urination after 1 and 3 months, respectively: Qmax - by 32.2% and 52.2%; Qave - by 24.2% and 37.9%; Vcomp - by 4.6% and 6.5% (not significant). Vres decrease by -49.5% and -75.6%. It was not only the improvement in digital uroflowmetry (UFM) indicators, but also in the type of the UFM curves. If, before the start of treatment UFM curves close to normal were observed in only 5.3% of patients, then at the end of study already in 44.2%. Combination therapy demonstrated a high degree of safety, although 26.9% of patients had concomitant diseases. During 3 months of treatment, only 5 adverse events were registered in 5 (2.5%) patients: dry mouth – 4 (2.0%), retrograde ejaculation – 1 (0.5%). Nobody interrupted treatment due to adverse events. There were no episodes of acute urinary retention. The program showed high satisfaction of doctors with the clinical effectiveness of treatment (4.5±0.9 on the Likert scale), as well as satisfaction of both doctors and patients with the tolerability of therapy (4.5±0.9 and 4.5±0.9 on the Likert scale), respectively. Conclusion. This study is original, both in terms of the combination of the used drugs and in terms of its design features. This is the first study of alfuzosin and solifenacin combination treatment in patients with LUTS/BPH with OAB and urgency. Also, this is the first study in which the factor of intravesical prostatic protrusion &gt; 10 mm was applied as a non-inclusion criterion. The therapy demonstrated: high and significant efficacy in relation to LUTS (irritative and obstructive), objective voiding parameters and impact on patient’s quality of life; high adherence to treatment, safety, tolerability and satisfaction with its results by doctors and patients. The effectiveness and safety of treatment in this study was achieved due to the combination of drugs used for the first time, careful selection of patients and exclusion of persons with severe mechanical bladder outlet obstruction from the observation group.

OTC SENIOR STATION: CONSUMER-FACING TECHNOLOGY TO PROMOTE MEDICATION SAFETY

Abstract Over-the-counter (OTC) medications with anticholinergic effects (e.g. doxylamine, diphenhydramine) are widely used by older adults, despite their association with an increased risk of Alzheimer’s disease and related dementias (ADRD). Authoritative bodies, such as the American Geriatrics Society and National Academy of Medicine, recommend discouraging the use of both prescription and OTC anticholinergics. However, most interventions previously developed and tested have targeted only prescription anticholinergics despite the use rate of OTC anticholinergics being higher in older adult populations. Consumer-facing technology may be ideal for addressing OTC anticholinergic use as it is cost effective, scalable, and can address the constraints of relying on busy pharmacists to intervene during older adult OTC medication purchases; this has become especially relevant as pharmacies face staffing shortages, increasing pharmacist workload and requiring pharmacies adjust their hours of operation. Our interdisciplinary team of pharmacists, engineers, and designers engaged both older adults and pharmacy staff in the co-design of “OTC Senior Station”: a user-centered, consumer-facing kiosk to be placed in community pharmacies to promote reduced anticholinergic use by older adults. Kiosk users are prompted to input brief information, which is used to present safer alternatives to OTC anticholinergics (e.g., for insomnia management). This poster will present OTC Senior Station--what we believe to be the first consumer-facing technology to target OTC anticholinergic use—the participatory design methods used to create it, and the results of studies to assess its usability with older adults.

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.

Clinical pharmacist-led assessment and management of anticholinergic burden and fall risk in geriatric patients

BackgroundThe aim of this study was to examine the risk of fall with the surrogate outcome of the Aachen Falls Prevention Scale and to assess the clinical pharmacist interventions in order to minimize anticholinergic drug burden and associated risk of fall according to a fall risk assessment scale in the older adults.MethodsPatients who admitted to the geriatric outpatient clinic of a university hospital and taking at least one anticholinergic drug were evaluated both retrospectively and prospectively as groups of different patients by the clinical pharmacist. Patients’ anticholinergic burden was assessed using the Anticholinergic Cognitive Burden Scale. For fall risk assessment, the Aachen Falls Prevention Scale was also administered to each patient whose anticholinergic burden was determined in the prospective phase of the study.ResultsA total of 601 patients were included. Risk of falls increased 2.50 times in patients with high anticholinergic burden (OR (95% CI) = 2.503 (1.071–5.852); p = 0.034), and the existing history of falls increased the risk of high anticholinergic burden 2.02 times (OR (95%CI) = 2.026 (1.059–3.876); p = 0.033). In addition, each unit increase in the fall scale score in the prospective phase increased the risk of high anticholinergic burden by 22% (p = 0.028). Anticholinergic burden was significantly reduced as a result of interventions by the clinical pharmacist in the prospective phase (p = 0.010).ConclusionOur study revealed that incorporating a clinical pharmacist in the handling of geriatric patients aids in the detection, reduction, and prevention of anticholinergic adverse effects.

Changes in Anticholinergic Burden in Parkinson’s Disease After Deep Brain Stimulation

ObjectiveThis 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 MethodsA 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). ResultsARS 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. ConclusionGPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

Efficacy of treatment of chronic obstructive pulmonary disease after virus-induced exacerbations

Viral respiratory infection is one of the main etiologic factors for acute exacerbations of COPD (AECOPD). The disease course after virus-associated AECOPD and the response to treatment have not been studied adequately.The aim was to evaluate the efficacy of single-inhaler triple therapy (SITT) of long-acting anticholinergic drugs (LAMA)/long-acting β2-agonists (LABA) of adrenergic receptors/inhaled glucocorticosteroids (ICS) on COPD symptoms, lung function, exercise tolerance, and inflammatory activity compared with multiple-inhaler triple therapy (MITT) after a virus-associated COPD exacerbation.Methods. This was an observational prospective cohort study of COPD patients (spirographус criterion) hospitalized for AECOPD with viral (n = 60) or viral-bacterial (n = 60) infection. The comparison group included patients with bacterial AECOPD (n = 60). Viral infection was diagnosed by PCR-RT of sputum or bronchoalveolar lavage fluid for RNAs of rhinovirus, RS virus, influenza A and B viruses, or SARS-CoV-2 virus. Bacterial infection was demonstrated by sputum purulence and/or procalcitonin test results and/or standard culture data. During AECOPD, blood cytokines were measured by ELISA. The patients were treated with SITT (investigational treatment) or MITT (comparison treatment) of LAMA/LABA/ICS in real-world clinical practice. The follow-up started 4 weeks after AECOPD regression and discharge from hospital.Results. After 52 weeks of treatment, FEV1 decline was smaller than in the SITT group. Differences from the MITT group were greater in patients with viral AECOPD (–69 (–75; –10) ml vs –75 (–78; –72) ml) or viral-bacterial AECOPD (–67.5 (–69; –37.25) ml vs –75.5 (–84; –70.25) ml). An increase in DLCO/Va, 6-minut walk test (6MWT) results, a decrease in bronchodilation coefficient, blood eosinophils and fibrinogen was seen only in subjects who received SITT and had viralor viral-bacterial AECOPD. A multiple regression model revealed a direct association between blood interleukin-5 and improvement in FEV1 (В = 0.848) and DLCO/Va (B=0.117) and a negative correlation with blood levels of amino-terminal propeptide of type-III procollagen and improvement in DLCO/Va (В = –0.021).Conclusion. SITT with LAMA/LABA/ICS was more effective in preventing FEV1 decline, increasing DLCO, 6MWT results, and decreasing airway inflammation in virus-associated or viral-bacterial AECOPD.

Effects of Probiotics Combined with Traditional Chinese Medicine, Acupressure Massage, and Acupuncture Point Application on Constipation

Psychoactive drugs have anticholinergic effects, which might cause constipation; however, probiotics and traditional Chinese medicine can resolve constipation. This study aimed to examine the effect of probiotics combined with traditional Chinese medicine, acupuncture point massage, and acupuncture point application on patients with intestinal solid heat constipation. We enrolled 200 patients, randomly divided into three intervention groups and a control group. Group 1 received probiotics combined with acupressure point massage and acupuncture point application; Group 2 received probiotics combined with acupressure point massage; Group 3 received probiotics combined with acupuncture point application, while the control group received routine treatment only. After intervention, the total effective rate of the intervention groups was higher than that of the control group (52%). The constipation symptom score in the intervention groups was lower than that in the control group, and the symptom score, defecation characteristics, and defecation time of group 1 were significantly lower than those of groups 2 and 3. The Bristol defecation trait, difficulty, time, and interval were better in the intervention groups than in the control group. Combining probiotics with traditional Chinese medicine, acupressure massage, and acupuncture point application can resolve intestinal solid heat constipation caused by psychoactive drugs.

Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment.

Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline. Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes. We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022. We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes. Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results. We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes. There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.

Polypharmacy in patients with dementia

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.

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.

Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

Association of anticholinergic drug exposure with the risk of dementia among older adults in Japan: The LIFE Study.

Several studies have investigated that anticholinergic drugs cause cognitive impairment. However, the risk of dementia associated with anticholinergics has not been extensively investigated in the super-aging society of Japan. We conducted this study to assess the association between anticholinergic drugs and the risk of dementia in older adults in Japan. This nested case-control study used data from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2020. We included 66,478 cases of diagnosed dementia and 328,919 matched controls aged ≥65years, matched by age, sex, municipality, and cohort entry year. Primary exposure was the total cumulative anticholinergic drugs prescribed from cohort entry date to event date or matched index date, which was the total standardized daily doses for each patient, calculated by adding the total dose of different types ofanticholinergic drugs in each prescription, divided by the World Health Organization-defined daily dose values. Odds ratios for dementia associated with cumulative exposure to anticholinergic drugs were calculated using conditional logistic regression adjusted for confounding variables. The mean (standard deviation) age at index date was 84.3 (6.9), and the percentage of women was 62.1%. From cohort entry date to event date or matched index date, 18.8% of the case patients and 13.7% of the controls were prescribed at least one anticholinergic drug. In the multivariable-adjusted model, individuals with anticholinergic drugs prescribed had significantly higher odds of being diagnosed with dementia (adjusted odds ratio, 1.50 [95% confidence interval, 1.47-1.54]). Among specific types of anticholinergic drugs, a significant increase in risk was observed with the use of antidepressants, antiparkinsonian drugs, antipsychotics, and bladder antimuscarinics in a fully multivariable-adjusted model. Several types of anticholinergic drugs used by older adults in Japan are associated with an increased risk of dementia. These findings suggest that the underlying risks should be considered alongside the benefits of prescribing anticholinergic drugs to this population.

P81: Anticholinergic Burden of Patients Assessed by UK Memory Clinics: An Audit

Objective:It is estimated that there are 55 million people living with dementias globally. With so few effective treatments available for dementias, it is vital that services optimise the management of risk factors for patients to slow their disease progression as much as possible. Commonly prescribed medications with anticholinergic effects can cause iatrogenic cognitive impairment and lead to faster decline in people living with dementia. United Kingdom (UK) national guidelines recommend minimising their use when assessing people with suspected dementia or during medication reviews of people with dementia. We proposed to audit how many people were being referred to memory assessment services in two UK locations with a significant anticholinergic burden, which medications were responsible, and whether this impacted on diagnosis.Methods:We developed an audit tool based on national guidelines to gather data on the age, gender, medications, diagnosis and cognitive impairment of the first 50 patients assessed in the Memory Assessment Services in Wolverhampton and Walsall in 2022. We used the anticholinergic effect on cognition scale (AEC) to measure patients’ anticholinergic burdens and identify the most frequently prescribed medications.Results:We collected data from 30 patients from Wolverhampton and 20 patients from Walsall. Across the two locations, only 10% presented with a significant anticholinergic burden, with 24% having some anticholinergic burden that was not considered significant. Every patient with a significant anticholinergic burden was later diagnosed with dementia.Most of the anticholinergic medications that were prescribed are generally prescribed for psychiatric or neurological indications and the most frequently prescribed drug was amitriptyline.Conclusion:The prescription of anticholinergic medications was not as prevalent as predicted in our sample. It may be that anticholinergic medication are less prescribed for physical illnesses as alternatives that do not cross the blood-brain barrier are available. Psychogeriatricians are well placed to review the anticholinergic medications that are commonly prescribed during the assessment of suspected dementia, due to their familiarity with these medications. In response to our findings, we plan to update our memory clinic assessment tools to highlight the need for clinicians to review patients’ anticholinergic burden during assessment.

Anticholinergic burden and polypharmacy in primary care referrals to tertiary outpatient clinics in Brazil

AbstractBackgroundAnticholinergic burden (ACB) and polypharmacy are associated with cognitive/functional impairment in the elderly and their frequency in primary care has been poorly studied in Brazil. We aimed to evaluate the frequency ACB/polypharmacy and association with cognitive impairment in two large tertiary care outpatients memory clinics in Brazil.MethodsWe retrospectively analyzed records of referrals from primary care to two tertiary outpatients memory clinics in Brazil (Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre and Hospital Santa Marcelina (HSM), São Paulo) from 2014 to 2022. Sociodemographic, clinical and medications in use in the first appointments were recorded. The ACB was calculated using the Brazilian Anticholinergic Activity Drug (BAAD) score, which classified drugs according to their central anticholinergic activity from 1 to 3, with higher values indicating greater anticholinergic activity. The BAAD score was dichotomized as = 0 or ≥ 1. Polypharmacy was defined as ≥ 5 drugs. A logistic regression was performed using age, sex, education, disease duration, dementia etiology, center and Mini Mental State Examination (MMSE) as covariates.ResultsAmong 980 referrals (HCPA = 429; HSM = 551), 602 (64.9%) had a final diagnosis of dementia, HCPA = 226 (56.1%); HSM = 376 (71.8%); p&lt;0.001. Alzheimer’s disease, 93 (21.7%) and multifactorial dementia, 109 (19.8%), was the most common dementia diagnosis in HCPA and HSM, respectively. Most patients, 666 (74%), had BAAD ≥ 1 and nearly half 438 (48.7%) had polypharmacy, with no difference between centers (Table 1). BAAD was not different between diagnoses, but polypharmacy was more frequent in vascular (71, 63.4%) and multifactorial (82, 59.9%) dementia. BAAD was associated with MMSE (OR 0.95, IC 95% 0.93‐0.97) and polypharmacy (OR 3.71, IC 95% 2.66‐5.24). In addition to BAAD, polypharmacy was also associated with female sex (OR 1.45, IC 95% 1.09‐1.91) and age (OR 1.01, IC 95% 1‐1.02).ConclusionMost patients referred from primary care were using some drug with anticholinergic activity and almost half had polypharmacy, which suggests liberality in the prescription of medications in this context.

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV.

This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV. This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study. Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype (FFP) based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs). Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22-1.32; 95% confidence interval (CI) range: 1.03-1.66), sedative burden (OR range: 1.18-1.24; 95% CI range: 1.02-1.45), high anticholinergic burden (OR range: 2.12-2.74; 95% CI range: 1.03-6.19), and high sedative burden (OR range: 1.94-2.18; 95% CI: 1.01-4.34). The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods.

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.