Anticholinergic Cognitive Burden Scale Research Articles

A - 2 Risk Factors for Reduced Mobility and Falls in Older Adults: the Role of Medication Use and Cognitive Impairment

Abstract Objective Sedative and anticholinergic (AC) medication use and cognitive impairment impose risk of gait imbalance and falls in older adults, but their combined effects on mobility have not been assessed. Method This cross-sectional study of 392 outpatients (age = 72 ± 7.7; 60.5%women; 93%White; education = 14 ± 3 years) characterized AC use (Anticholinergic Cognitive Burden Scale [ACB]) and number of sedative medications. Balance confidence (Activities-specific Balance Confidence Scale), walking decline compared to 5 years prior (0–3 scale), and recurrent falls (dichotomized by ≥2) were self-reported. Neuropsychological performance was averaged into a norm-adjusted composite (COG). T-tests and Pearson correlations assessed bivariate relationships across medication use, COG, and mobility. Multivariate models regressed falls, balance confidence, and gait changes (in separate models) on COG and medication use (ACs and sedatives examined separately), controlling for covariates. Results Most patients (70%–85%) used ≥1 sedative or AC medication. Few (12%) reported recurrent falls (range = 0–30), but balance confidence was reduced (M = 77.68 ± 21.31%) with mild walking declines reported (M = 1.34 ± 1.03). More sedative medication use and higher ACB scores were bivariately related to worse COG and mobility, and stronger COG was associated with better mobility (p’s ≤ 0.004). Worse COG (β = 0.196, p = 0.002) and more medication use, both sedatives (β = −0.246, p = 0.002) and ACB (β = −0.147, p = 0.047), independently predicted worse balance confidence. Higher ACB (β = 0.182, p = 0.022) and worse COG (β = −0.193, p = 0.007) uniquely predicted walking decline. Each sedative medication increased odds of falls by 27.4% (adjOR = 1.274, p = 0.034). Conclusion AC/sedative medication use and cognitive impairment pose complementary risks for compromised mobility. Clinicians should be alert to AC/sedative use and cognitive impairment in older patients at risk of falls.

Prevalence of strong anticholinergic use in residents with and without cognitive impairment and frailty: Analysis from 106 nursing homes in 12 Asia-Pacific and European countries

PurposeThere is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty. MethodsSecondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0–2 (non-frail), 3–6 (frail) and 7–14 (most-frail). Data were analyzed using descriptive statistics. ResultsOverall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %). ConclusionsOne in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm.

Drugs with Anticholinergic Properties and Association with Hip Fractures in Older Patients: A Danish Nationwide Cohort-Study.

Hip fractures (HFx) resulting from falls are a significant health concern, and drugs with anticholinergic properties (DAP) increase the risk of falls. This study aimed to assess the association between use of DAP at hospital admission and HFx risk in older patients. This nationwide population-based study included all patients ≥65 years admitted to Danish geriatric wards during 2005-2014. Outcome of interest was first HFx within 2-years follow-up. The Anticholinergic Cognitive Burden (ACB) scale quantified DAP use. Cox regression analysis of data from four national registries was adjusted for activities of daily living, age, marital status, admission year, BMI, fracture history, previous admissions, dementia, anti-osteoporotic drugs, and Charlson comorbidity index. 74,589 patients (62.8% female) were included, 45,463 (60.9%) received DAP at index, and 7,861 HFx occurred during follow-up. Cumulative 2-year HFx hazard was highest for ACB=0 (15.3%). Higher ACB-score was not associated with increased HFx risk in univariable nor multivariable analyses. In sensitivity analysis, use of DAP with high anticholinergic burden (≥2) did not alter results. In this high-incidence national cohort, higher ACB-score was not associated with increased HFx risk. Our results call for further research on association between specific DAP and risk of HFx.

Assessing the anticholinergic cognitive burden classification of putative anticholinergic drugs using drug properties.

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

Sedative load and anticholinergic burden among older adults in Slovenia over a decade: Potential for optimization of pharmacotherapy.

This study investigates the 10-year trend in the sedative and anticholinergic burden among older adults in Slovenia, with the aim of identifying opportunities to optimize pharmacotherapy in this population. A retrospective drug utilization analysis was conducted based on a national anonymized database of dispensed prescriptions from 2009 to 2019. The study employed the sedative load model and the anticholinergic cognitive burden scale to assess the sedative and anti cholinergic burden, respectively. The findings indicate that in 2019, 45.6 % and 40.8 % of older adults (≥ 65 years) used sedative and anticholinergic medications, respectively. A high sedative load and a clinically significant anticholinergic burden were observed in a considerable proportion of older adults (13.2 % and 11.2 %, respectively, in 2019). The age-standardized prevalence of sedative load and anti-cholinergic burden significantly decreased over the 10-year study period by 5.6 % and 1.7 %, respectively (absolute difference), while the prevalence of clinically significant anticholinergic burden remained stable. Notably, the age groups 85-89 years and above 90 years had an increase in the proportion of individuals with a clinically significant anticholinergic burden over the years. These results emphasize the need for targeted interventions, particularly in the oldest age groups, to promote safe and effective medication use among older adults.

Modeling the effects of treatment resistance and anticholinergic burden on cognitive function domains in patients with schizophrenia

The contribution of anticholinergic burden to cognitive function in patients with treatment resistant schizophrenia (TRS) is uncertain. This case-control study aims to comprehensively examine the association between treatment resistance and cognitive functions and the contribution of anticholinergic burden in patients with schizophrenia. Anticholinergic burden of all patients was calculated using the Anticholinergic Cognitive Burden scale. Exploratory Factor Analysis of 11 cognitive assessments identified four cognitive domains: verbal memory, attention and general cognitive functions, visual memory and processing speed, and executive function. Two structural equation models (SEM) examined the relationship of TRS and these cognitive functions with, and without considering anticholinergic burden. A total of 288 participants were included (TRS N=111, non-TRS N=177). Patients with TRS performed poorer than the non-TRS group only in the executive function domain. Anticholinergic burden contributed significantly to the attention and general cognitive functions, visual memory and processing speed, and executive function. The impact of TRS on executive function was no longer significant after adding anticholinergic burden to the SEM. Results suggested that anticholinergic burden contributes to a wide range of cognitive function impairment in patients with schizophrenia and is likely to be part of the apparent differences of cognitive function between TRS and non-TRS.

Anticholinergic Medication Burden and Cognitive Subtypes in Parkinson's Disease without Dementia.

Cognitive changes are heterogeneous in Parkinson's disease (PD). This study compared whether anticholinergic burden drives differences in cognitive domain performance and empirically-derived PD-cognitive phenotypes. A retrospective chart review contained participants (n = 493) who had idiopathic PD without dementia. Participants' medications were scored (0-3) and summed based on the anticholinergic cognitive burden scale (ACBS). We examined the ACBS' relationship to five cognitive domain composites (normative z-scores) and three (K-means clustering based) cognitive phenotypes: cognitively intact, low executive function (EF), and predominately impaired EF/memory. Analyses included Spearman correlations, analysis of covariance, and Pearson chi-squared test. Overall, phenotypes did not differ in anticholinergic burden, and (after false-discovery-rate corrections) no cognitive domains related. When comparing those above and below the clinically relevant ACBS cutoff (i.e., score ≥3), no significant phenotype or domain differences were found. Anticholinergic medication usage did not drive cognitive performance in a large clinical sample of idiopathic PD without dementia.

Anticholinergic burden and the cognitive functions in elderly and senile patients with arterial hypertension

The aim of the study was to evaluate the effect of anticholinergic load (AHN) on cognitive functions (CF) in elderly and senile multimorbid patients with arterial hypertension (AH).Materials and methods. 330 patients aged 60 years and older with essential AH were included in the study (median age 79 [72; 84] years, 158 (51 %) of women). All the patients were underwent the assesment of CF using the Montreal Cognitive Assessment Scale (MoCA), Mini-Mental Status Scale (MMS), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog), Trial Making Test (TMT), Digit Symbol Substitution Test (DSST), Verbal Association Test (literal (letter) and categorical (animal) associations), Boston Naming Test (BNT), Word-Color Interference Test, Stroop colorword conflict test. The anticholinergic load was determined using the anticholinergic load scale (Anticholinergic Cognitive Burden Scale, ACB).Results. Compared with patients who do not take anticholinergic drugs, multimorbid elderly and senile hypertensive patients with 2 or more points on the ACB scale had significantly lower final scores on the MoCA test (23 [21; 24.3] versus 24 [22; 25] points, respectively, p=0.042) and on MMSE (26 [24; 29] vs. 27.5 [25; 29] points, respectively, p=0.015), they spent statistically more time completing part B of the TMT test (217.5 [187.3; 246.3] vs. 204 [166.8; 247.3] seconds, respectively, p=0.038). The difference between the execution time of part B and part A of the TMT test in patients with 2 or more points on the ACB scale was statistically significantly greater than in patients with 0 points on this scale (141 [103.8; 168.5] versus 124 [83.8; 162] sec, respectively, p=0.034). Age, gender, education, and the structure of concomitant diseases did not differ between the groups.Conclusion. The results obtained indicate the adverse effect of аnticholinergic вurden on CF of multimorbid elderly and senile hypertensive patients and dictate the need to optimize pharmacotherapy in this category of patients.

Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birthcohortanalysis, aimed to determine if repeated exposure to anticholinergic medicationswas associated with greater decline, and whether decline was reversed with medication reduction. From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified bythe Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantifiedby theWord Learning Test [WLT], and processing speed quantified by theTimed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms. Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p<0.01). Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.

Anticholinergic and sedative medication use in older patients with cognitive concerns.

Anticholinergic (AC) and sedative medications are a risk factor for cognitive impairment. This study sought to characterize AC and sedative use in older patients seen for outpatient neuropsychological evaluation and evaluate their associations with different cognitive domains. We hypothesized that AC and sedative use would be associated with worse attention/processing speed (AP), executive functioning (EF), and memory. We conducted a cross-sectional chart review of 392 patients (mean [M] age = 72 ± 7.7 years, range = 54-91). Medications were characterized by number of AC medications (≥1 on the Anticholinergic Cognitive Burden Scale [ACB]), number of sedative medications, and polypharmacy (≥5 daily medications). Demographically adjusted composites were calculated for AP, EF, and memory. Bivariate Pearson correlations assessed relationships between medication use and cognition. Multivariate linear regressions evaluated significant medication-cognition associations, controlling for total medications, medical comorbidities, and estimated premorbid cognitive functioning. Polypharmacy was common (80%; n = 314). Most patients (70%; n = 275) used ≥1 sedative medications (range = 0-9). Over half (63%; n = 248) used ≥1 AC drugs (range = 0-7), yet ACB scores were ≤2 in 74% of patients. Sedative use was negatively correlated with AP (r = -0.134, p = 0.008) and EF (r = -0.105, p = 0.04). ACB scores were negatively correlated with AP (r = -0.106, p = 0.037). Sedatives and a priori covariates significantly predicted AP performance (R2 = 0.127, p < 0.001); using more sedative medications was uniquely associated with worse AP (β = -0.426, p = 0.049). No significant associations were found with memory. AC and sedative medications and polypharmacy were prevalent in this sample of older patients. Though both drug classes had negative relationships with AP and EF, sedatives had a particularly negative association with AP. Contrary to our hypotheses, memory was not associated with medication use; however, anticholinergic burden was low within the sample, and AP and EF deficits may masquerade as memory problems.

Adverse effects associated with long-term use of anticholinergics amongst older adults with intellectual disability: a longitudinal cohort study

Abstract Introduction Intellectual disability defined as “a condition characterized by significant limitation in both intellectual functioning and adaptive behaviour that originates before the age of 22”.[1] Older adults with intellectual disability are exposed to high anticholinergic burden, due to the high prevalence of neurological and mental health diseases compared to the general older adult population. The long-term use of anticholinergics is associated with adverse effects such as decline in physical function, cognitive function and higher risk of dementia and Alzheimer disease in the general population. However, a recent scoping review found that there are no longitudinal studies examining adverse effects associated with long-term use of anticholinergics amongst older adults with intellectual disability.[2] Aim To examine adverse effects associated with long-term use of medication with anticholinergic activity among older adults with intellectual disability. Methods This study examined older adults with intellectual disability aged 40 or over, who participated in wave 1 (2010-11) (W1) and wave 4 (2019-20) (W4) in the Intellectual Disability Supplement to the Irish Longitudinal Study on Aging (IDS-TILDA). Anticholinergic burden was quantified using the Anticholinergic Cognitive Burden (ACB) Scale. Participants were categorised into three groups based on their total ACB score: no exposure (ACB = 0), mild exposure (ACB 1-4) and high exposure (ACB = 5+). Logistic regression used to examine adverse effects reported at W4 associated with ACB score captured at W1. Reported anticholinergic adverse effects were constipation, falls, edentulous, Barthel Index for activity of daily livings, mental health conditions and dementia/Alzheimer’s. The logistic regression model was adjusted for age, gender, level of intellectual disability, residence, epilepsy, and polypharmacy excluding anticholinergic medications. Results 506 people with intellectual disability participated and 487 (96.24%) provided medication data at both waves. At W1, 30% had no exposure (ACB=0), 40% had mild exposure (ACB = 1-4) and 30% had high ACB score (ACB = 5+). At W4, there was an increase by 5% of those with mild ACB and a reduction of 1.5% and 3.5% in those with no exposure and high ACB exposure respectively. Participants with high ACB score at W1, were significantly associated with falls (OR = 1.97, 95% CI 1.20-3.54), reporting mental conditions (OR = 14.78, 95% CI 7.84 - 27.86) and dementia, Alzheimer’s or taking anti-dementia drugs (N06D) (OR = 0.21, 95% Cl 0.07 - 0.67) at W4, compared to those with no anticholinergic exposure. Conclusion The long-term use of anticholinergics was associated with physical and mental adverse effects, and therefore the possibility of anticholinergic deprescribing should be explored and examined to enhance appropriate medicine use among older adults with intellectual disability. This is the first study examined the impact of long-term anticholinergic use among this population. However, further anticholinergic adverse effects should be addressed in future such as decline in cognitive function and frailty.

Classification system for primary care provider eConsults about medications for older adults with frailty

BackgroundProviding primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability.MethodsA classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case.ResultsThe classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications.ConclusionA classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services.

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

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. 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. 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). 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.

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

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. 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. 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 burdenduring 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.

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.

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.

The complex relationship between anticholinergic medication, frailty, and hospitalization in patients with early‐stage dementia

AbstractBackgroundAnticholinergic medications are associated with frailty and hospitalization in patients with dementia. It is unclear if anticholinergic burden mediates the relationship between frailty and hospitalization or if specific dementia syndromes moderate the direct and indirect relationships between these three factors.MethodWe analyzed electronic health record and claims data for member‐patients diagnosed with dementia with Lewy bodies (DLB), Alzheimer’s disease (AD), or vascular dementia (VD) from an integrated healthcare system in the U.S. between October 2015 and August 2022. The Anticholinergic Cognitive Burden Scale (ACB), Claims‐based Frailty Index (frail ≥0.20), and number of hospital admissions were calculated for the 12‐month period prior to dementia diagnosis. Patient demographics, ACB score, frailty status, and hospitalization frequency were compared between dementia syndromes. Baron and Kenny regression‐based method was used to evaluate if ACB is a mediator between frailty and hospitalization. DLB, AD, and VD were included as interactions with ACB and frailty in stratified mediation models to determine if dementia syndrome moderated the relationship. Significant interaction terms indicate a moderating effect of dementia syndrome. All models included patient age and sex as covariates.ResultWe identified 3166 patients (DLB n = 175; AD n = 2478; VD n = 513). Approximately 23% of patients with DLB were prescribed 5+ anticholinergic medications (17.2% with VD; 9.9% with AD; p&lt;.001). Two or more hospitalizations were documented in 12.5% of patients with VD (10.3% with DLB; 5.5% with AD; p&lt;.001). The ACB score was 3.7 greater for patients with frailty compared to those without (3.2, 4.4, p&lt;.001). The relationship between frailty and hospitalization was mediated by ACB (higher ACB was associated with increased utilization; Table 1). A diagnosis of AD or VD moderated the indirect relationship between frailty and hospitalization, but the specific dementia syndrome did not moderate the path between ACB and hospitalization (Table 2; Figure 1).ConclusionIn the year prior to dementia diagnosis, frailty was associated with a higher number of anticholinergic medications, which, in turn, was associated with a greater number of hospitalizations. A diagnosis of VD increased the expected rates of hospitalization for frail patients, while an AD diagnosis decreased the magnitude of the association between frailty and hospitalization.

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.

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

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. 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. 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. 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.