Anticholinergic Drugs and Their Effects on Delirium and Mortality in the Elderly

Aim: To investigate the use of drugs with anticholinergic properties (DAPs) and their associations with delirium and mortality among elderly patients with comorbidities. Methods: 425 patients (≧70 years of age) in geriatric wards and nursing homes were assessed. The use of DAPs was retrieved from their medical records. Delirium was diagnosed according to the DSM-IV criteria. Results: Of the 341 patients (80.2%) treated with multiple DAPs (≧2), 92 patients (27.0%) suffered from delirium, whereas 14 of 84 patients (16.7%) without DAP treatment had delirium (p = 0.050). In a logistic regression analysis with age, gender, and Charlson Comorbidity Index as covariates, DAP treatment did not predict delirium (odds ratio 1.67, 95% confidence interval 0.87–3.21). The 2-year mortality was 49.3% (n = 168) in DAP users and 35.7% (n = 30) in non-users, respectively (p = 0.026). In the Cox proportional hazard model adjusted for age, gender, and comorbidity, DAPs did not predict mortality (hazard ratio 1.12, 95% confidence interval 0.75–1.68). Conclusion: The use of DAPs is very frequent among frail inpatients with comorbidities, but their use has no independent prognostic significance

Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population study.

BACKGROUND: Studies have raised concerns that medications with anticholinergic property have potential adverse effects on health outcomes. OBJECTIVES: The objective of this study is to examine the prospective relationships between total anticholinergic burden (ACB) from medications and mortality, and cardiovascular disease (CVD) in a general population. DESIGN: Observational study. SETTING: Community cohort. SUBJECTS: We examined data collected from 21,636 men and women without cancer at the baseline who participated in a baseline survey 1993-97 in the European Prospective Investigation into Cancer (EPIC)-Norfolk. They were followed until 2009/11. METHODS: We performed Cox-proportional hazards models to determine the associations between total ACB and the subsequent risk of all-cause mortality and incident CVD during the follow-up. RESULTS: There were a total of 4,342 people died and 7,328 had an incident CVD during the study follow-up (total person years=322,321 years for mortality and 244,119 years for CVD event). Compared with people with no anticholinergic burden (ACB=0), people with total ACB≥3 from medications had hazards ratios of 1.83 (1.53, 2.20) and 2.17 (1.87, 2.52) for mortality and CVD incidence outcomes, respectively, after adjusting for potential confounders. Repeating the analyses after excluding people with prevalent illnesses, and events occurring within the first 2 years of follow-up, only slightly attenuated the results. CONCLUSION: There appear to be a class effect as well as dose-response relationship between the ACB and both outcomes. Future research should focus on understanding the relationship between ACB and mortality, and cardiovascular disease and possibly minimising ACB load where feasible

Co-morbidity and drug treatment in Alzheimer's disease. A cross sectional study of participants in the Dementia Study in Northern Norway

Inappropriate medical treatment of co-morbidities in Alzheimer’s disease (AD) is an increasing concern in geriatric medicine. The objective of this study was to compare current drug use related to co-morbidity between individuals with a recent diagnosis of AD and a cognitively healthy control group in a population based clinical trial in Northern Norway. Setting: Nine rural municipalities with 70 000 inhabitants in Northern Norway. Participants: Participants with and without AD recruited in general practice and by population based screening. 187 participants with a recent diagnosis of AD were recruited among community dwellers. Of 791 respondents without cognitive symptoms, 500 were randomly selected and invited to further clinical and cognitive testing. The final control group consisted of 200 cognitively healthy individuals from the same municipalities. Demographic characteristics, data on medical history and current medication were included, and a physical and cognitive examination was performed. The statistical analyses were carried out by independent sample t-test, chi-square, ANCOVA and logistic regression. A co-morbidity score was significantly higher in AD participants compared to controls. The mean number of drugs was higher for AD participants compared to controls (5.1 ± 3.6 and 2.9 ± 2.4 respectively, p < 0.001 age and gender adjusted), also when adjusted for co-morbidity. AD participants used significantly more anticholinergic, sedative and antidepressant drugs. For nursing home residents with AD the mean number of drugs was significantly higher compared to AD participants living at home (6.9 ± 3.9 and 4.5 ± 3.3, respectively, p < 0.001). AD participants were treated with a significantly higher number of drugs as compared to cognitively healthy controls, even after adjustment for co-morbidity. An inappropriate use of anticholinergic and sedative drugs was identified, especially among nursing home residents with AD. The drug burden and the increased risk of adverse reactions among individuals suffering from AD need more attention from prescribing doctors

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly

Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people’s drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents’ quality of life and use of health services.</p> <p><b>Methods and design</b></p> <p>During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months.</p> <p>The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations.</p> <p><b>Discussion</b></p> <p>To our knowledge, this is the first large-scale randomized trial exploring whether relatively light intervention, that is, staff training, will have an effect on reducing harmful drugs and improving QOL among institutionalized older people.</p> <p><b>Trial registration</b></p> <p>ACTRN12611001078943</p