Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.

BACKGROUND: Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs. METHODS: A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens. RESULTS: The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden during the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score > 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia. Most of these findings remained consistent with multinomial logistic regression.  CONCLUSION: Four out of five older adults with AD had some level of anticholinergic burden, with over 60% having moderate-high anticholinergic burden. Several predisposing, enabling, and need factors were associated with the cumulative anticholinergic burden. The study findings suggest a critical need to minimize the cumulative anticholinergic burden to improve AD care.

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

BACKGROUND: The 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. METHODS: Patients 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. RESULTS: A 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). CONCLUSION: Our study revealed that incorporating a clinical pharmacist in the handling of geriatric patients aids in the detection, reduction, and prevention of anticholinergic adverse effects.

Comparative safety of antimuscarinics versus mirabegron for overactive bladder in Parkinson disease.

BACKGROUND: Overactive bladder (OAB) is a common non-motor symptom of Parkinson disease (PD), often treated with antimuscarinics or beta-3 agonists. There is lack of evidence to guide OAB management in PD. OBJECTIVES: To assess the comparative safety of antimuscarinics versus beta-3 agonists for OAB treatment in PD. METHODS: We employed a new-user, active-comparator cohort study design. We included Medicare beneficiaries age ≥65 years with PD who were new users of either antimuscarinic or beta-3 agonist. The primary outcome was any acute care encounter (i.e., non-elective hospitalization or emergency department visit) within 90 days of OAB drug initiation. The main secondary outcome was a composite measure of acute care encounters for anticholinergic related adverse events (AEs). Matching on high-dimensional propensity score (hdPS) was used to address potential confounding. We used Cox proportional hazards models to examine the association between OAB drug category and outcomes. We repeated analyses for 30- and 180-day follow-up periods. RESULTS: We identified 27,091 individuals meeting inclusion criteria (mean age: 77.8 years). After hdPS matching, antimuscarinic users had increased risks for any acute care encounter (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.12-1.37) and encounters for anticholinergic related AEs (HR 1.18, 95% CI 1.04-1.34) compared to beta-3 agonist users. Similar associations were observed for sensitivity analyses. CONCLUSIONS: Among persons with PD, anticholinergic initiation was associated with a higher risk of acute care encounters compared with beta-3 agonist initiation. The long-term safety of anticholinergic vs. beta-3 agonist therapy in the PD population should be evaluated in a prospective study.

Changes in the Use of Long-Term Medications Following Incident Dementia Diagnosis.

Importance: Dementia is a life-altering diagnosis that may affect medication safety and goals for chronic disease management. Objective: To examine changes in medication use following an incident dementia diagnosis among community-dwelling older adults. Design, Setting, and Participants: In this cohort study of adults aged 67 years or older enrolled in traditional Medicare and Medicare Part D, patients with incident dementia diagnosed between January 2012 and December 2018 were matched to control patients based on demographics, geographic location, and baseline medication count. The index date was defined as the date of first dementia diagnosis or, for controls, the date of the closest office visit. Data were analyzed from August 2021 to June 2023. Exposure: Incident dementia diagnosis. Main Outcomes and Measures: The main outcomes were overall medication counts and use of cardiometabolic, central nervous system (CNS)-active, and anticholinergic medications. A comparative time-series analysis was conducted to examine quarterly changes in medication use in the year before through the year following the index date. Results: The study included 266 675 adults with incident dementia and 266 675 control adults; in both groups, 65.1% were aged 80 years or older (mean [SD] age, 82.2 [7.1] years) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs 48.39%) and anticholinergic medications (17.79% vs 15.96%) and less likely to use most cardiometabolic medications (eg, diabetes medications, 31.19% vs 36.45%). Immediately following the index date, the cohort with dementia had a greater increase in mean number of medications used (0.41 vs -0.06; difference, 0.46 [95% CI, 0.27-0.66]) and in the proportion of patients using CNS-active medications (absolute change, 3.44% vs 0.79%; difference, 2.65% [95% CI, 0.85%-4.45%]) owing to an increased use of antipsychotics, antidepressants, and antiepileptics. The cohort with dementia also had a modestly greater decline in use of anticholinergic medications (quarterly change in use, -0.53% vs -0.21%; difference, -0.32% [95% CI, -0.55% to -0.08%]) and most cardiometabolic medications (eg, quarterly change in antihypertensive use: -0.84% vs -0.40%; difference, -0.44% [95% CI, -0.64% to -0.25%]). One year after diagnosis, 75.2% of the cohort with dementia were using 5 or more medications (2.8% increase). Conclusions and Relevance: In this cohort study of Medicare Part D beneficiaries, following an incident dementia diagnosis, patients were more likely to initiate CNS-active medications and modestly more likely to discontinue cardiometabolic and anticholinergic medications compared with the control group. These findings suggest missed opportunities to reduce burdensome polypharmacy by deprescribing long-term medications with high safety risks or limited likelihood of benefit or that may be associated with impaired cognition.

Despite Recommendations, Anticholinergics Account for the Majority of Prescriptions to Treat Overactive Bladder in the United States.

IMPORTANCE: There are significant associations between anticholinergic medication use and an increased risk of cognitive impairment and dementia. Many experts now advocate minimizing the use of anticholinergic medications to treat overactive bladder (OAB) in elderly women. OBJECTIVE: The aim of this study was to describe temporal and geographic trends in the pharmacologic treatment of OAB for patients 65 years or older across the United States. STUDY DESIGN: The U.S. Centers for Medicare & Medicaid Services publishes annual Medicare Provider Utilization and Payment Data. The data set includes the number of unique Part D beneficiaries 65 years or older with at least 1 claim for a drug and the number of 30-day fills dispensed. The database also includes the U.S. state and rural-urban commuting area designation of the prescriber. RESULTS: From 2013 to 2019, Medicare Part D beneficiaries 65 years or older received 47.7 million 30-day fills for the treatment of OAB. In 2013, anticholinergics represented 98% of the total 30-day fills (5.6 million) for OAB. The use of ß3 agonists was nearly 24 times greater in 2019 than in 2013. Geographic variation in prescribing practices was evident. CONCLUSIONS: The number of anticholinergics dispensed for the treatment of OAB remained relatively stable, and there was a substantial increase in the use of ß3 agonists. Percentages of anticholinergics dispensed varied among states. More patients are being treated for OAB; however, anticholinergics comprised the majority of prescriptions for treatment in 2019.

HIV-positive women have higher prevalence of comorbidities and anticholinergic burden: assessment of the HIV-positive population from Menorca (Balearic Islands).

Currently, the management of comorbidities and polypharmacy in HIV-infected patients requires a coordinated action, with special focus on gender differences. Observational, cross-sectional study was conducted to study the HIV population from Menorca (Illes Balears). Adult HIV-positive individuals on antiretroviral treatment attending the pharmacy service from Hospital Mateu Orfila (Menorca) were included. In a single visit, demographical and clinical characteristics, comorbidities and cotreatments were collected. Anticholinergic burden (Drug Burden Index, DBI), drug-to-drug interactions (BOT PLUS database) and symptoms associated with HIV treatment (HIV-SI index) were assessed. A total of 223 patients were included, 68.2% men, with a median age of 53.00 (44.50-58.00) years, median BMI of 24.07, 47.73% smokers and 9.90% drug consumers. Women had more advanced stages of the disease and significantly more symptoms (cough and anxiety) versus men (p = .033 and p = .048, respectively). Moreover higher exposures to anticholinergic drugs (DBI 0.51 vs. 0.27) were reported, together with more frequency of drug-to-drug interactions (57.7% vs. 37.5%; p = .005) that increased with age. Red interactions were more frequently reported in PI (2.69%), NNRTIs (1.92%) and booster drugs (1.92%). These results support the need to implement specific measures for the management of HIV-infected women and tools to assess polypharmacy and risk of drug-to-drug interactions.

Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: Potential deprescribing cascade.

BACKGROUND: Polypharmacy may result from inappropriate prescribing of medications to treat adverse drug reactions (ADRs), i.e., "prescribing cascade." A potentially harmful prescribing cascade affecting those with severe dementia can result when anticholinergics are prescribed to manage side effects of cholinesterase inhibitors (ChEIs). We investigated 1) factors associated with co-prescribing of anticholinergics and ChEIs and 2) whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics-a potentially beneficial reversal or "deprescribing cascade." METHODS: We conducted a retrospective analysis of linked Medicare Part A/B/D claims, Master Beneficiary Summary File, Minimum Data Set, Area Health Resource File, and Nursing Home Compare from 2015 to 2016. Subjects were Medicare beneficiaries residing in nursing homes, ≥65 years old with severe dementia admitted for non-skilled stays, who were prescribed ChEIs. Cross-sectional analysis evaluated factors associated with co-prescribing of anticholinergics with ChEIs. Longitudinal Cox proportional hazards regression examined whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics over a 1-year period. RESULTS: We found 15% of our sample experienced co-prescribing of anticholinergics and ChEIs. Several resident and facility-level factors were associated with co-prescribing anticholinergics. Advancing age, minority race or ethnicity, end-stage renal disease, heart failure, and poor appetite were associated with a decreased likelihood of co-prescribing. Female sex, polypharmacy, and non-geriatric prescriber-type were associated with a higher likelihood of co-prescribing. In longitudinal analyses, we observed that discontinuation of ChEIs was associated with a reduced likelihood (HR 0.58 [95% CI, 0.47-0.71]) of discontinuing any medications with anticholinergic properties, except for bladder antimuscarinics (HR 1.32 [95% CI, 0.83-2.09]). CONCLUSIONS: Younger, healthier older adults with dementia were more likely to experience co-prescribing anticholinergics and ChEIs. Discontinuation of anticholinergics was infrequent. Further research is needed to understand prescribers' ability to recognize and reverse potential prescribing cascades through deprescribing.

[Use of anticholinergic drugs among the elderly and a comparison between risk scales: a population-based study]. / Uso de medicamentos com ação anticolinérgica em idosos e comparação entre escalas de risco: estudo de base populacional.

The pattern of morbidity and mortality has changed in recent years due to the increase in chronic noncommunicable diseases, leading to multiple comorbidities and the use of several medications. The scope of the study was to evaluate the anticholinergic drugs used by elderly people, according to risk scales. It involved a population-based cross-sectional study with elderly people. Socioeconomic factors, health problems, and medication use were investigated in the previous 15 days. The Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Cognitive Burden Scale (ACB) were used for risk classification according to anticholinergic activity of the drugs. A total of 1451 elderly people were interviewed and 1305 used medications, 60.7% of which with anticholinergic action, especially among the 80-year-old age bracket and the less educated. In total, 5703 drugs were used, 1282 (22.5%) of which with anticholinergic action. Kappa agreement of 0.63 was observed when assessing the ACB and ADS risk scales. The prevalence of the use of drugs with anticholinergic action was high, and attention should be paid to the consequences related to their use, with a view to more rational decision-making in clinical practice.

O padrão de morbimortalidade tem-se modificado nos últimos anos com aumento das doenças crônicas não-transmissíveis levando a múltiplas comorbidades e ao uso de muitos medicamentos. O objetivo foi avaliar o uso de medicamentos com ação anticolinérgica por idosos. Estudo transversal de base populacional, com indivíduos de 60 anos ou mais. Foram investigados fatores socioeconômicos, problemas de saúde e utilização de medicamentos nos últimos 15 dias. Para a classificação dos medicamentos com atividade anticolinérgica foram utilizadas as escalas: Anticholinergic Drug Scale (ADS), Anticholinergic Risc Scale (ARS), Anticolinergic Cognitive Burden Scale (ACB). Entrevistados 1.451 idosos, destes, 1.305 utilizaram medicamentos, sendo que 60,7% usaram fármacos com ação anticolinérgica, sobretudo aqueles com mais de 80 anos e os menos escolarizados. No total, 5.703 medicamentos foram usados, 1.282 (22,5%) com ação anticolinérgica. Observou-se concordância kappa de 0,63 quando se avaliou as escalas de risco ACB e ADS. A prevalência de uso de fármacos com ação anticolinérgica foi alta, deve-se estar atento às consequências relativas ao seu uso, tendo em vista a tomada de decisão mais racional na prática clínica.

Uso de medicamentos com ação anticolinérgica em idosos e comparação entre escalas de risco: estudo de base populacional / Use of anticholinergic drugs among the elderly and a comparison between risk scales: a population-based study

Resumo O padrão de morbimortalidade tem-se modificado nos últimos anos com aumento das doenças crônicas não-transmissíveis levando a múltiplas comorbidades e ao uso de muitos medicamentos. O objetivo foi avaliar o uso de medicamentos com ação anticolinérgica por idosos. Estudo transversal de base populacional, com indivíduos de 60 anos ou mais. Foram investigados fatores socioeconômicos, problemas de saúde e utilização de medicamentos nos últimos 15 dias. Para a classificação dos medicamentos com atividade anticolinérgica foram utilizadas as escalas: Anticholinergic Drug Scale (ADS), Anticholinergic Risc Scale (ARS), Anticolinergic Cognitive Burden Scale (ACB). Entrevistados 1.451 idosos, destes, 1.305 utilizaram medicamentos, sendo que 60,7% usaram fármacos com ação anticolinérgica, sobretudo aqueles com mais de 80 anos e os menos escolarizados. No total, 5.703 medicamentos foram usados, 1.282 (22,5%) com ação anticolinérgica. Observou-se concordância kappa de 0,63 quando se avaliou as escalas de risco ACB e ADS. A prevalência de uso de fármacos com ação anticolinérgica foi alta, deve-se estar atento às consequências relativas ao seu uso, tendo em vista a tomada de decisão mais racional na prática clínica.

Abstract The pattern of morbidity and mortality has changed in recent years due to the increase in chronic noncommunicable diseases, leading to multiple comorbidities and the use of several medications. The scope of the study was to evaluate the anticholinergic drugs used by elderly people, according to risk scales. It involved a population-based cross-sectional study with elderly people. Socioeconomic factors, health problems, and medication use were investigated in the previous 15 days. The Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Cognitive Burden Scale (ACB) were used for risk classification according to anticholinergic activity of the drugs. A total of 1451 elderly people were interviewed and 1305 used medications, 60.7% of which with anticholinergic action, especially among the 80-year-old age bracket and the less educated. In total, 5703 drugs were used, 1282 (22.5%) of which with anticholinergic action. Kappa agreement of 0.63 was observed when assessing the ACB and ADS risk scales. The prevalence of the use of drugs with anticholinergic action was high, and attention should be paid to the consequences related to their use, with a view to more rational decision-making in clinical practice.

Association between anticholinergic drug burden with sarcopenia, anthropometric measurements, and comprehensive geriatric assessment parameters in older adults.

BACKGROUND: Older patients use multiple drugs due to their comorbidities and most of these drugs have anticholinergic drug burden (ADB). We aimed to investigate the association between ADB and sarcopenia, anthropometric measurements, and comprehensive geriatric assessment (CGA) parameters in older adults. METHODS: Patients ≥65 years who applied to geriatrics outpatient clinic between January 2019-March 2020 were included. Patients with cognitive dysfunction were excluded. CGA tests were conducted on patients. Handgrip strength (HGS), bioelectrical impedance analysis (BIA), and a 6-meter walking test were used for sarcopenia definition. The Anticholinergic Cognitive Burden (ACB) scale was used to calculate the ADB. RESULTS: Totally 256 patients (women/men:180/76) were included. The mean age was 82±6.8. Two groups were created as without ADB (n=116) and with ADB (n=140). Sarcopenia was higher in the ADB group (p=0.04). In women and men as ADB increased HGS decreased (respectively; p=0.023 r=-0.170, p=0.031 r=-0.248) and Basic Activities of Daily Living (BADL) test score increased (respectively; p= <0.001 r= 0.292, p=0.04 r= 0.244). In the linear regression (LR) analysis age and BADL test score had significant association with ADB in women (respectively; p=0.001, p=0.023). CONCLUSION: The finding that sarcopenia is higher in the patients with ADB and HGS decreases as ADB increases, suggesting that ADB may be a risk factor for sarcopenia by decreasing HGS. Also, it has been determined that, especially in older women, as ADB increases, the dependence on basic daily living activities increases.

Use of tricyclic antidepressants and other anticholinergic medicines by older Aboriginal Australians: association with negative health outcomes.

BACKGROUND: Aboriginal and Torres Strait Islander Australians have a relatively high prevalence of multimorbidity requiring treatment with medications. This study examines medication use and anticholinergic burden (ACB) among a cohort of older Aboriginal and Torres Strait Island people. METHOD: This cross-sectional study involving five Aboriginal communities (two in metropolitan Sydney and three on the mid-north coast of New South Wales) used a structured interview process to assess cognition, depression, and activities of daily living for a cohort of older adults (aged 60 years and over). Participants also reported on their health status, medical history, and prescription medications during the interview. ACB was calculated, and its association with adverse health outcomes including cognitive impairment, falls, hospitalization, and depressive symptoms were examined. RESULTS: Most participants (95%) were taking at least one regular medication with polypharmacy (≥5 medications) observed in 43% of participants; 12.2% had a significant ACB (≥3) with antidepressants being a major contributor. Anticholinergic medication use was associated with cognitive impairment, recent hospitalization (past 12 months), and depressive symptoms. After controlling for age, sex, and comorbidity, only the presence of depressive symptoms remained significantly associated with the use of anticholinergic medication (odds ratio 2.86; 95% confidence interval 1.48-5.51). CONCLUSIONS: Clinically significant ACB was common in older Aboriginal Australians and was largely attributable to inappropriate use of tricyclic antidepressants. Greater awareness of medication-related risk factors among both health care professionals and Aboriginal communities can play an important role in improving health and quality of life outcomes.

A 12-Year Retrospective Study of the Prevalence of Anticholinergic Polypharmacy and Associated Outcomes Among Medicare Patients with Overactive Bladder in the USA.

BACKGROUND AND OBJECTIVE: Antimuscarinics, drugs with anticholinergic properties, are frequently prescribed for overactive bladder, and anticholinergic burden is associated with adverse events. The "Polypharmacy: Use of Multiple Anticholinergic Medications in Older Adults" (Poly-ACH) measure was developed by the Pharmacy Quality Alliance and is used by the Centers for Medicare and Medicaid Services. Using the Poly-ACH measure, we assessed the prevalence of anticholinergic polypharmacy among Medicare patients in the USA with overactive bladder and determined associations between polypharmacy and medical conditions, care, and spending. METHODS: This was a retrospective cohort study of Medicare beneficiaries with overactive bladder (coverage period: 2006-2017). Anticholinergic polypharmacy, measured by the Poly-ACH, was defined as concurrent use of two or more anticholinergics, each with two or more prescription claims on different dates of service for ≥ 30 cumulative days. Change in annual frequency of anticholinergic polypharmacy was assessed using logistic regression. Associations between anticholinergic polypharmacy over 3 years and falls, fractures, mental status, and medical care spending were assessed with longitudinal regression models. RESULTS: In total, 226,712 patients contributed 940,201 person-years of follow-up after overactive bladder diagnosis. The share of patients meeting the Poly-ACH definition was 3.3% in 2006 and 1.7% in 2017. Women and nursing home residents had higher risks of anticholinergic polypharmacy. Having 1 year or more of positive Poly-ACH status in the 3 years prior was associated with higher rates of all outcomes. CONCLUSIONS: Anticholinergic polypharmacy was uncommon among older adults with overactive bladder. Prevalence was higher among women and nursing home residents, and it was associated with negative outcomes, highlighting potential longitudinal implications of anticholinergic burden.

A comparison of anticholinergic burden in older patients with and without cancer.

Aim: To compare anticholinergic burden (ACB) in older patients with and without cancer and evaluate the effects of ACB on geriatric syndromes. Methods: A total of 291 patients from the geriatric clinic and 301 patients from the oncology clinic were evaluated. ACB <2 was categorized as low ACB and ACB ≥2 was categorized as high ACB. A comprehensive geriatric assessment was performed on patients from the geriatric clinic. Results: ACB scores were significantly higher in patients without cancer compared with those with cancer (p < 0.005). Number of falls and Geriatric Depression Scale 15 scores were higher and Mini-Nutritional Assessment and Barthel/Lawton activities of daily living scores were lower in geriatric patients with high ACB scores compared with those with low ACB scores (p < 0.005). Conclusion: It is crucial to understand the potential effects of ACB for rational drug use and optimum cancer management in older patients with cancer.

Lay abstract The elderly population is increasing rapidly worldwide, and most cancer patients are over the age of 65. In this age group, preexisting medical conditions other than cancer lead to the use of multiple drugs, which is defined as polypharmacy. Additionally, the anticholinergic burden (ACB) of the drugs affects cancer treatment in the elderly. This study investigated the frequency of polypharmacy and ACB in elderly patients with and without cancer and their relationship with geriatric syndromes such as depression, falls, nutritional and cognitive impairments. We found that ACB was higher in older patients without cancer than those with cancer and is related to increased falls, depressive symptoms, and impaired nutritional and functional status in older patients. Given the prevalence of cancer among older adults, it is crucial to understand the potential effects of the ACB for rational drug use and optimum cancer management in older patients with cancer.

Effects of anticholinergic and sedative medication use on fractures: A self-controlled design study.

BACKGROUND/OBJECTIVES: Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1-year fall-related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures. DESIGN: A retrospective cohort study with nested self-controlled analyses conducted between January 1, 2014, and December 31, 2016. SETTING: Twenty percent nationwide, random sample of US Medicare beneficiaries. PARTICIPANTS: New users of medications with anticholinergic/sedating properties who were 66+ years old and had Medicare Parts A, B, and D coverage but no claims for medications with anticholinergic/sedating properties in the year before initiation were eligible. MEASUREMENTS: We followed new users of medications with anticholinergic/sedating properties until first non-vertebral, fall-related fracture (primary outcome), Medicare disenrollment, death, or end of study data. We estimated the 1-year risk with corresponding 95% confidence intervals (CIs) of first fracture after new use. We applied the self-controlled case-crossover and case-time-control designs to estimate odds ratios (ORs) and 95% CIs by comparing anticholinergic and/or sedating medication exposure (any vs. none) during a 14-day hazard period preceding the fracture to exposure to these medications during an earlier 14-day control period. RESULTS: A total of 1,097,989 Medicare beneficiaries initiated medications with anticholinergic/sedating properties in the study period. The 1-year cumulative incidence of fall-related fracture, accounting for death as a competing risk, was 5.0% (95% CI: 5.0%-5.0%). Using the case-crossover design (n = 41,889), the adjusted OR for the association between anticholinergic/sedating medications and fractures was 1.03 (95% CI: 0.99, 1.08). Accounting for the noted temporal trend using the case-time-control design (n = 209,395), the adjusted OR was 1.60 (95% CI: 1.52, 1.69). CONCLUSION: Use of anticholinergic/sedating medication was temporally associated with an increased odds of fall-related fractures. Patients and their healthcare providers should consider pharmacologic and non-pharmacologic treatments for the target condition that are safer.

Anticholinergic burden: First comprehensive analysis using claims data shows large variation by age and sex.

PURPOSE: The cumulative effect of medication inhibiting acetylcholine activity-also known as anticholinergic burden (AB)-can lead to functional and cognitive decline, falls, and death. Given that studies on the population prevalence of AB are rare, we aimed to describe it in a large and unselected population sample. METHODS: Using the German Pharmacoepidemiological Research Database (GePaRD) with claims data from ~20% of the German population we analyzed outpatient drug dispensations in 2016. Based on the Anticholinergic Cognitive Burden (ACB) scale, we classified persons into four categories and determined the cumulative AB as continuous variable. RESULTS: Among 16,470,946 persons (54% female), the prevalence of clinically relevant AB (ACB≥3) was 10% (women) and 7% (men). Below age 40 it was highest in persons ≤18 years (6% both sexes). At older ages (50-59 vs. 90-99 years), prevalence of ACB≥3 increased from 7% to 26% (men) and from 10% to 32% (women). Medication classes contributing to the cumulative AB differed by age: antihistamines, antibiotics, glucocorticoids (≤19 years), antidepressants (20-49 years), antidepressants, cardiovascular medication, antidiabetics (50-64 years), and additionally medication for urinary incontinence/overactive bladder (≥65 years). Medication dispensed by general physicians contributed most to the cumulative AB. CONCLUSION: Although a clinically relevant AB is particularly common in older persons, prevalence in younger age groups was up to 7%. Given the risks associated with AB in older persons, targeted interventions at the prescriber level are needed. Furthermore, risks associated with AB in younger persons should be explored.

Prevalence and Factors Associated with Cumulative Anticholinergic Burden Among Older Long-Stay Nursing Home Residents with Overactive Bladder.

BACKGROUND: Overactive bladder (OAB), the primary cause of urinary incontinence in nursing homes, is commonly treated with anticholinergic medications; however, the elderly population is vulnerable to the adverse effects associated with anticholinergic burden. Given the relatively high prevalence of OAB among nursing home residents, it is important to understand the magnitude of anticholinergic burden in this population. OBJECTIVES: The objectives of this study were to (1) examine the prevalence of cumulative anticholinergic burden among long-stay nursing home (LSNH) residents with OAB; and (2) identify the factors associated with varying levels of cumulative anticholinergic burden. METHODS: This was a retrospective, cohort study using Minimum Data Set-linked Medicare claims data. Anticholinergic burden was determined based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using defined daily dose. The Andersen Behavioral Model framework was used to identify the predisposing, enabling, and need factors associated with levels of anticholinergic burden. Multivariable logistic regression models were developed to determine the factors associated with levels of anticholinergic burden. RESULTS: A total of 123,308 LSNH residents with OAB were identified; 87.2% had some degree of anticholinergic burden and 27.3% had high cumulative burden. Multiple factors were associated with higher levels of burden, including younger age, female sex, and non-Hispanic White ethnicity (predisposing factors); dual eligibility, Southern geographic region, and rural residence (enabling factors); and a number of comorbidities and concomitant medications (need factors). CONCLUSIONS: This study revealed a high level of anticholinergic burden among LSNH residents. Multiple factors were associated with a high level of burden. There is a need to optimize the use of anticholinergics due to their significant safety concerns in the LSNH setting.

Exposure to Anticholinergic and Sedative Drugs and Healthcare Costs in Older Patients with Neurocognitive Disorders.

BACKGROUND: Literature supports an increasing number of older patients living with neurocognitive disorders alongside with their annual worldwide costs. Therapeutic management of behavioral and psychological symptoms includes the use of anticholinergic and sedative drugs for which significant exposure is negatively associated with clinical outcomes. OBJECTIVE: The aim of this study was to assess the healthcare costs differences related to an increase in the exposure to anticholinergic and sedative drugs in older patients with neurocognitive disorder. METHODS: A longitudinal study was conducted during 3 years on 1,604 participants of the MEMORA cohort linked with both regional public health insurance and hospital discharge databases between 2012 and 2017. Direct medical and non-medical costs were included. Exposure to anticholinergic and sedative drugs was measured by the drug burden index (DBI). RESULTS: Costs difference associated with a DBI≥0.5 were + 338€ (p < 0.001). After adjustment on comorbidities, NCD stage, cognitive impairment, functional limitation, polypharmacy, and sociodemographic characteristics, a DBI≥0.5 was found to be an independent predictor of an increase of total healthcare costs by 22%(p < 0.001). CONCLUSION: Anticholinergic and sedative drugs have a substantial economic burden among older patients with neurocognitive disorder. More studies are required to assess the clinical and economic impact of an efficient strategy based on the reduction of the exposure to anticholinergic and sedative drugs and the promotion of non-pharmacological interventions.

Rethinking Second-Line Therapy for Overactive Bladder to Improve Patient Access to Treatment Options.

Idiopathic overactive bladder (OAB) is a chronic condition that negatively affects quality of life, and oral medications are an important component of the OAB treatment algorithm. Recent literature has shown that anticholinergics, the most commonly prescribed oral medication for the treatment of OAB, are associated with cognitive side effects including dementia. ß3-adrenoceptor agonists, the only alternative oral treatment for OAB, are similar in efficacy to anticholinergics with a more favorable side effect profile without the same cognitive effects. However, there are marked cost variations and barriers to access for OAB medications, resulting in expensive copays and medication trial requirements that ultimately limit access to ß3-adrenoceptor agonists and more advanced procedural therapies. This contributes to and perpetuates health care inequality by burdening the patients with the least resources with a greater risk of dementia. When prescribing these medications, health care professionals are caught in a delicate balancing act between cost and patient safety. Through multilevel collaboration, we can help disrupt health care inequalities and provide better care for patients with OAB.

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries.

PURPOSE: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). METHODS: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 < DBI ≤ 1, 1 < DBI ≤ 2, and DBI > 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 < DBI≤1) DBI drug exposure. RESULTS: The distribution of the mean daily DBI, aggregated at the month-level, was: 58.1% DBI = 0, 29.0% 0 < DBI≤1, 9.3% 1 < DBI≤2, and 3.7% DBI > 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. CONCLUSIONS: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events.