Anticholinergic Cognitive Burden Research Articles

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.

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.

Pharmacist-guided deprescribing for frail older adults in nursing homes using STOPPFrail

Abstract Introduction Frail older adults in nursing homes are often prescribed inappropriate medications. Whilst STOPPFrail can aid deprescribing in such persons with limited life expectancy, there has been insufficient research showing pharmacists’ application of this tool.[1,2] Aim To evaluate the impact of pharmacist-led application of STOPPFrail to frail older nursing home residents. Methods Nursing home residents aged ≥65 years with advanced frailty and a poor one-year survival prognosis were eligible to partake.[1] A convenience sample of nursing homes was recruited via nursing home GPs within the research team’s professional network. After recruitment by their general practitioner (GP), a research pharmacist (EH) reviewed participants using STOPPFrail to identify potentially inappropriate medications (PIMs). Deprescribing recommendations for each participant were provided to GPs via email and discussed via videoconference, whereby recommendations were implemented if GPs perceived they were clinically appropriate. Outcome measures were recorded at baseline, post intervention, and at six months. Descriptive and inferential statistics were performed, where p&amp;lt;0.05 represents a statistically significant difference from baseline. Results Ninety-nine patients from six nursing homes were recruited (76% female). The mean age was 86 years (standard deviation [SD]: 6.9), and the mean number of comorbidities was 15 (SD: 5.3). Nearly all patients (94%) were prescribed ≥1 PIM at baseline. From 349 clinically relevant STOPPFrail recommendations to deprescribe 329 PIMs, 58% were accepted (n=203) and 55% were implemented (n=193), resulting in 176/329 PIMs (53%) being deprescribed – with 167/176 (95%) persisting at six months. Recommendations most commonly concerned medications without a clear indication (29.5%), vitamin D (16.9%), antipsychotics (8.9%), memantine (7.2%), and proton pump inhibitors (7.2%). Relating to baseline, post intervention, and at six months: i)the mean ± SD number of prescribed medications was 16.0±6.1, 14.6±5.7 (p&amp;lt;0.01), and 15.4±5.5 (p=0.03); ii)the monthly mean ± SD cost of patients’ medications was €186.8±123.7, €172.7±119.0 (p&amp;lt;0.01), and €186.4±121.2 (p=0.949); iii)the mean ± SD Modified Medication Appropriateness Index (MMAI) was 2.19±0.73, 2.11±0.74 (p&amp;lt;0.01), and 2.08±0.71 (p&amp;lt;0.01); iv)the median [interquartile range] Drug Burden Index (DBI) was 1.03 [0.50-2.00], 0.93 [0.50-1.80] (p&amp;lt;0.01), and 0.93 [0.50-1.80] (p&amp;lt;0.01); v)the mean ± SD Anticholinergic Cognitive Burden (ACB) was 4.27±2.45, 3.86±2.54 (p&amp;lt;0.01), and 3.94±2.70 (p=0.03). The mean ± SD EQ-5D-5L QoL summary score was 0.183±0.286 at baseline and 0.159±0.312 (p=0.18) at six months. The mean ± SD EQ-5D-5L visual analogue score was 60.3±22.8 at baseline and 61.8±19.9 (p=0.45) at six months. Over two-thirds of residents (70/99) were alive at six months. There were 36 falls, one emergency department visit, and eight non-elective hospitalisations six months prior to baseline compared to 31, four, and seven respectively in the six months post intervention. Conclusion To the authors’ knowledge, this is the first study to apply STOPPFrail to residents of long-term care facilities and also the first to have a pharmacist do so. Although this study lacked a control group, the intervention significantly reduced PIMs, medication costs (initially, but not maintained at follow-up), and both the anticholinergic and sedative burden. The intervention maintained QoL and reduced fall frequency. Given these results, policymakers, nursing home facilities, and clinicians should consider the wider implementation of pharmacist-led STOPPFrail-guided reviews to optimise the medications of frail older adults.

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.

Eye movements as predictor of cognitive improvement after cognitive remediation therapy in patients with schizophrenia.

Baseline cognitive functions of patients predicted the efficacy of cognitive remediation therapy (CRT), but results are mixed. Eye movement is a more objective and advanced assessment of cognitive functions than neuropsychological testing. We aimed to investigate the applicability of eye movements in predicting cognitive improvement after patients with schizophrenia were treated with CRT. We recruited 79 patients with schizophrenia to complete 8 weeks of CRT and assessed their cognitive improvement outcomes. Eye movements were assessed by prosaccades, antisaccades, and free-viewing tasks at baseline, and neuropsychological tests in four cognitive domains were assessed before and after treatment to calculate treatment outcomes. Predictors of demographic information, clinical characteristics, and eye movement measures at baseline on cognitive improvement outcomes were analyzed using logistic regression analysis. We further compared the predictive performance between eye movement measurements and neuropsychological test regarding the effect of CRT on cognitive improvement, and explored factors that could be affect the treatment outcomes in different cognitive domains. As operationally defined, 33 patients showed improved in cognition (improved group) and 46 patients did not (non-improved group) after CRT. Patients with schizophrenia being employed, lower directional error rate in antisaccade task, and lower the gap effect (i.e., the difference in saccadic latency between the gap condition and overlap condition) in prosaccade task at baseline predicted cognitive improvement in CRT. However, performance in the free-viewing task not associated with cognitive improvement in patients in CRT. Our results show that eye-movement prediction model predicted the effect of CRT on cognitive improvement in patients with schizophrenia better than neuropsychological prediction model in CRT. In addition, baseline eye-movements, cognitive reserve, antipsychotic medication dose, anticholinergic cognitive burden change, and number of training sessions were associated with improvements in four cognitive domains. Eye movements as a non-invasiveness, objective, and sensitive method of evaluating cognitive function, and combined saccadic measurements in pro- and anti-saccades tasks could be more beneficial than free-viewing task in predicting the effect of CRT on cognitive improvement in patients with schizophrenia.

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.

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.

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 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 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.

Factors Associated with Acute Injurious Falls in Elderly Hospitalized Patients: A Multicenter Descriptive Study.

The Centers for Medicare & Medicaid Services Hospital-Acquired Conditions (CMS-HAC) links Medicare payments to health care quality. Experiencing a serious disability or death associated with a fall in a health care facility based on diagnosis codes has been identified as an opportunity for improvement. Multiple factors contribute to an inpatient fall, including medications that affect cognition in older adults. The primary aim of this study was to investigate the effect of the commonly prescribed classes of medications on the CMS-HAC falls and trauma definition in US hospitals in a large inpatient database from 2019 to 2021. The authors analyzed data from 835 hospitals in the Vizient Clinical Data Base between January 1, 2019, and December 31, 2021, on patients ≥ 65 years of age with CMS-HAC patient falls and trauma codes. Using logistic regression and stepwise Poisson regression analysis, the authors identified demographic, clinical, and hospital-related variables associated with falls meeting the CMS-HAC definition. The top 20 prescribed drug classes in these patients were also identified. Among 11,064,024 patient encounters, 5,978 met the CMS-HAC definition of a serious fall. Patients who experienced a serious fall were significantly more likely to be > 79 years of age (p < 0.001, odds ratio [OR] 1.30, 95% confidence interval [CI] 1.23-1.37), have a history of prior falls (p < 0.001, OR 2.30, 95% CI 2.11-2.50), have a code for dementia (p < 0.001, OR 1.50, 95% CI 1.40-1.60), and have higher anticholinergic cognitive burden (ACB) scores (p < 0.001, OR 1.14, 95% CI 1.13-1.14). Specific medication classes associated with CMS-HAC falls were first-generation antihistamines (p < 0.00, OR 1.21, 95% CI 1.09-1.35), second-generation antihistamines (p ≤ 0.001, OR 1.15, 95% CI 1.13-1.19), and atypical antipsychotics (p < 0.001, OR 1.18, CI 1.13-1.29). Patients who experience a fall meeting the CMS-HAC fall definition are significantly more likely to have a prior history of falling, dementia, and a higher ACB score. Results from this study may inform future quality improvement work aimed at reducing injurious falls.

Prevalence of the consumption of anticholinergic drugs in HIV patients

ObjectiveTo analyse anticholinergic agent consumption in HIV patients 50 years or older; to determine anticholinergic risk using the Anticholinergic Cognitive Burden Scale (ACB) and Anticholinergic Risk Scale (ARS); and to determine if these patients use any type of benzodiazepine. MethodA descriptive observational study of 256 HIV patients 50 years or older. Results73.1% were men. Mean age was 56 ± 5.9 years. 55.9% of the patients were coinfected with HCV. Excluding HIV drugs, mean drug consumption was 2.9 ± 2.9 drugs per patient. The ACB and ARS scales showed that 26.2% and 17.2% of the patients took an anticholinergic agent, and that 43.3% and 36.4% presented high anticholinergic risk, respectively. 30.5% of patients consumed benzodiazepines. ConclusionsThe percentage of HIV patients aged 50 years or older who were taking anticholinergic agents was statistically significantly higher on the ACB scale than on the ARS scale. No studies are available on the HIV population with which to compare our results, but there is evidence that this group of drugs can affect older adults.

Risk factors for dementia in Parkinson's Disease - the overuse of anticholinergic drugs.

To determine the risk factors for dementia in a group of patients with Parkinson's Disease (PD), especially the effect of the anticholinergic burden assessed according to the Anticholinergic Cognitive Burden scale (ACB) and the CRIDECO Anticholinergic Load Scale (CALS). To provide information about factors associated with Parkinson's Disease dementia (PDD), especially the anticholinergic burden and testing the effect of both scales in an assessment of the anticholinergic burden in this group of patients. A retrospective and cross-sectional analysis of medical records of patients with Parkinson's Disease admitted to the Neurology Department of the Medical University of Silesia, Katowice, Poland between 2019 and 2021 was performed. We found 418 patients with a diagnosis of PD, but 80 were excluded due to lack of a cognitive function assessment. Based on MMSE score, the remaining 338 patients were divided into two groups of patients with, and without, PDD. Next, demographic and clinical data was collected. The anticholinergic burden was assessed using the ACB and the CALS scales. According to the authors of these scales, : if a scale score is of three or more points, this should be considered as a significant anticholinergic burden. Multiple logistic regression with backward elimination was used to assess factors significantly related to the presence of dementia, and two different models were used for both scales assessing the anticholinergic burden. 62 (18.3%) patients were diagnosed with PDD. Overall significant anticholinergic burden (≥ 3 points) was found in 31.95% of patients using CALS and in 18.93% using ACB. Anticholinergic burden was higher in patients with dementia (CALS 50 vs. 27.90%, p < 0.001, ACB 43.5 vs. 13.41%, p < 0.001). According to both models, the factors significantly related to dementia were: age (ACB OR 1,114 (1.062-1.170), p < 0.001, CALS OR 1.123 (1.070-1.178), p < 0.001), significant anticholinergic burden (ACB OR 3.433 (1.746-6.750), p < 0.001, CALS OR 2.166 (1.157-4.055), p = 0.016) disease severity in the Hoehn-Yahr scale (ACB OR 1.752 (1.197-2.565), p = 0.004, CALS OR 1.831 (1.256-2.670), p = 0.002) and atrial fibrillation (ACB OR 5.593 (1.417-22.083), p = 0.014, CALS OR 5.159 (1.314-20.254), p = 0.016). The anticholinergic burden is larger in PDD patients compared to PD patients without dementia. CALS or ACB scales are helpful in this risk assessment and might be crucial to avoid the development of PDD, especially in older PD patients with multimorbidities.

Low-Income Older Adults' Vulnerability to Anticholinergic Medication-Associated Frailty.

A growing body of research supports the negative impact of anticholinergic drug burden on physical frailty. However, prior research has been limited to homogeneous white European populations, and few studies have evaluated how anticholinergic burden tools compare in their measurement function and reliability with minority community-dwelling adult populations. This study investigated the association between anticholinergic drug exposure and frailty by conducting a sensitivity analysis using multiple anticholinergic burden tools in a diverse cohort. A comprehensive psychometric approach was used to assess the performance of five clinical Anticholinergic Burden Tools: Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), average daily dose, total standardized daily doses (TSDD), and Cumulative Anticholinergic Burden scale (CAB). Spearman correlation matrix and intraclass correlation coefficients (ICC) were used to determine the association among the variables. Ordinal logistic regression is used to evaluate the anticholinergic burden measured by each scale to determine the prediction of frailty. Model performance is determined by the area under the curve (AUC). The cohort included 80 individuals (mean age 69 years; 55.7% female, 71% African American). All anticholinergic burden tools were highly correlated (p < 0.001), ICC3 0.66 (p < 0.001, 95% confidence interval (CI) 0.53-0.73). Among individuals prescribed anticholinergics, 33% were robust, 44% were prefrail, and 23% were frail. All five tools predicted prefrail and frail status (p < 0.05) with low model misclassification rates for frail individuals (AUC range 0.78-0.85). Anticholinergic burden tools evaluated in this cohort of low-income African American older adults were highly correlated and predicted prefrail and frail status. Findings indicate that clinicians can select the appropriate instrument for the clinic setting and research question while maintaining confidence that all five tools will produce reliable results. Future anticholinergic research is needed to unravel the association between interventions such as deprescribing on incident frailty in longitudinal data.