The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. Chronic exposure to anticholinergic medications adversely affects the course of Alzheimer disease. A Pilot Randomized Clinical Trial Utilizing the Drug Burden Index to Reduce Exposure to Anticholinergic and Sedative Medications in Older People Anticholinergic Drugs and Physical Function Among Frail Elderly Population Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study. Anticholinergic drug use and negative outcomes among the frail elderly population living in a nursing home. Use of medications with anticholinergic properties and cognitive function in a young-old community sample. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. Estrogen Treatment Effects on Anticholinergic-Induced Cognitive Dysfunction in Normal Postmenopausal Women Systematic Overview of Cochrane Reviews for Anticholinergic Effects of Antipsychotic Drugs Anticholinergic medications in community-dwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and adverse drug events. Changes in anticholinergic load from regular prescribed medications in palliative care as death approaches Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs? Controlled clinical trial of sedative-anticholinergic drugs in patients with the irritable bowel syndrome. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. Evaluation of antitussive agents in man.
Anticholinergic  Drug Scale ( ADS ) scores were previously associated with serum anticholinergic activity ( SAA ) in a pilot study . To replicate these results , the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long-term care facility residents who were not included in the pilot study . Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects . In the replication analysis , ADS scores were significantly associated with SAA ( R2 = .0947 , P < .0001 ) . In the modification analysis , each model significantly predicted SAA , including ADS scores ( R2 = .0741 , P < .0001 ) . The modifications examined did not appear useful in optimizing the ADS . This study replicated findings on the association of the ADS with SAA . Future work will determine whether the ADS is clinical ly useful for preventing anticholinergic adverse effects OBJECTIVE Authors examined the effect of chronic exposure to anticholinergics in a cohort of Alzheimer disease ( AD ) patients . METHODS All patients were examined annually with st and ard neuropsychologic tests and received the cholinesterase inhibitor donepezil hydrochloride at a dose of 10 mg/day . The study population ( N=69 ) was divided into two groups : those receiving one or more concomitant medications with significant anticholinergic properties ( N=16 ) and those receiving no concomitant medications with anticholinergic properties ( N=53 ) . RESULTS At 2 years , MMSE scores were significantly worse for patients receiving anticholinergic medications than for those not on anticholinergics . CONCLUSION Although very preliminary , these data suggest that concomitant therapy with anticholinergics may be associated with significant deleterious effects on acetylcholinesterase therapy , or , more speculatively , that chronic exposure to anticholinergics may have adverse effects on the clinical course of AD Background : The drug burden index ( DBI ) is an evidence -based tool that utilizes pharmacologic principles to calculate an individual 's total exposure to anticholinergic and sedative medications . Higher DBI has been associated with functional impairment in observational studies of older people . Objective : To assess the impact of providing information about DBI to general practitioners ( GPs ) on prescribing for older people . Methods : This was a cluster r and omized controlled trial with 3 months of follow-up . Participants were volunteers aged ≥70 years , living in self-care retirement villages in Sydney , Australia . The study intervention involved a letter and phone call to GPs , using DBI to prompt them to consider cessation or dose reduction of anticholinergic and sedative medications . The primary study outcome was to assess the impact of information about DBI on prescribing practice s of the GPs . Results : A total of 115 participants were enrolled , 57 in the intervention group ( from 6 sites ) and 58 in the control group ( from 6 sites ) . At baseline , 19 of 57 participants in the intervention group and 31 of 58 participants in the control group had a DBI > 0 ( p < 0.05 ) . At follow-up , a DBI change was observed in 16 participants . DBI decreased in 12 participants , 6 ( 32 % ) in the intervention group , and 6 ( 19 % ) in the control group . GPs identified the following barriers to reducing anticholinergic and sedative drugs : uncomfortable altering prescriptions initiated by specialists ; unable to influence patients ' attitudes ; unaware of patients ' medications and strong clinical indication . Conclusions : The intervention targeting GPs ' prescribing practice s was less effective than anticipated in reducing anticholinergic and sedative drug exposure , and barriers were identified . Future studies should explore multidisciplinary interventions , engaging patients , specialists , GPs , and pharmacists Increasing evidence from experimental studies and human observations suggests that drugs with anticholinergic properties can cause physical and mental impairment . The aim of this study was to evaluate the relationship between the use of drugs with anticholinergic activity and measures of physical performance , muscle strength , and functional status in persons aged 80 years or older . Data are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study . The ilSIRENTE study is a prospect i ve cohort study performed in the mountain community living in the Sirente geographic area ( L'Aquila , Abruzzo ) in Central Italy .  Physical performance was assessed using the physical performance battery score ( Short Physical Performance Battery ) , which is based on three timed tests : 4‐meter walking speed , balance , and chair st and tests . Muscle strength was measured by h and grip strength . We defined as anticholinergic drugs all medications for which serum anticholinergic activity was previously demonstrated . Analyses of covariance were performed to evaluate the relationship of anticholinergic drugs with physical function . In the unadjusted model , all the physical performance , muscle strength , and functional measures showed significant associations with the anticholinergic drug use . After adjustment for potential confounders ( age , gender , smoking , physical activity level , cognitive performance score , living alone , body mass index , congestive heart failure , lung diseases , diabetes ) , these associations were weaker but still statistically significant ( physical performance battery score : non‐users anticholinergic drugs 6.9 , SE 0.1 , users anticholinergic drugs 6.1 , SE 0.2 , P=0.05 ; h and grip strength : non‐users anticholinergic drugs 31.3 kg , SE 0.8 , users anticholinergic drugs 28.8 kg , SE 1.0 , P=0.05 ; Activities of Daily Living scale score : non‐users anticholinergic drugs 1.2 , SE 0.1 , users anticholinergic drugs 1.6 , SE 0.1 , P=0.03 ; Instrumental Activities of Daily Living scale score : non‐users anticholinergic drugs 2.7 , SE 0.1 , users anticholinergic drugs 3.4 , SE 0.1 , P<0.001 ) . The use of medication with anticholinergic properties is common among community older subjects in Italy . Our results suggest that among old‐old subjects the use of anticholinergic drugs is associated with impaired physical performance and functional status INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial AIM Increasing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment . The aim of the present study was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older nursing home residents . METHODS We used data from the data base of the U.L.I.S.S.E project ( Un Link Informatico sui Servizi Sanitari Esistenti per l'Anziani ) , a prospect i ve multicenter observational study . Patients from 31 facilities in Italy were assessed at baseline and at 6 and 12 months by trained personnel , using the Minimum Data Set for Nursing Home ( MDS-NH ) . The only exclusion criterion was age younger than 65 years . The Anticholinergic Risk Scale ( ARS ) , a list of commonly prescribed drugs with potential anticholinergic effects , was used to calculate the anticholinergic load . RESULTS A total population of 1490 patients was analyzed ; almost half of the sample ( 48 % ) was using drugs with anticholinergic properties . The population of patients with ARS 1 or higher had a higher comorbidity index ( P < .003 ) and greater cognitive impairment ( CPS 5 - 6 ) ( P < .007 ) . They were more likely to suffer from heart failure , Parkinson disease , depression , anxiety , and schizophrenia . In multivariate analysis , a higher score in the ARS scale was associated with a greater likelihood of functional decline ( described as the loss of ≥1 ADL point ) ( odds ratio [ OR ] 1.13 ; confidence interval [ CI ] 1.03 - 1.23 ) , to a higher rate of falls ( OR 1.26 ; CI 1.13 - 1.41 ) , and to a higher incidence of delirium ( OR 1.16 ; CI 1.02 - 1.32 ) during a 1-year follow-up . CONCLUSIONS The use of medications with anticholinergic properties is common among older nursing home residents . Our results suggest that among older nursing home residents the use of anticholinergic drugs is associated with important negative outcomes , such as functional decline , falls , and delirium OBJECTIVES To examine whether anticholinergic medications have effects on the level of cognitive function or cognitive decline  in persons in their early to mid 60s . METHODS A r and omly selected community-based sample of 2058 persons aged 60 - 64 at baseline was interviewed twice over four years . Anticholinergic medication use was determined from self-report medication data using the Anticholinergic Drug Scale . Cognition was assessed with the California Verbal Learning Test I ( one trial ) , Digits Backwards , the Symbol Digit Modalities Test , the Mini-Mental State Exam and simple and choice reaction time .  Persons meeting criteria for Mild Cognitive Impairment were identified in a clinical sub study . Mixed models adjusting for age , sex , self-rated depression and physical health , and total number of medications were used to analyse the data . RESULTS There was a significant main effect of anticholinergic group averaged across time for the Symbol Digits Modalities Test with poorer performance among anticholinergic medication users . Main effects for the other cognitive tests and mild cognitive impairment were non-significant . No time by anticholinergic group interactions were significant . CONCLUSIONS This study suggests that exposure to anticholinergic medication is associated with lower level of complex attention in the young-old , but not with greater cognitive decline over time . Although the clinical significance of this is not clear , caution should be taken when prescribing medications with anticholinergic effects to older persons Abstract Objective To assess the potential of anticholinergic drugs as a cause of  non-degenerative mild cognitive impairment in elderly people . Design Longitudinal cohort study . Setting 63 r and omly selected general practice s in the Montpellier region of southern France . Participants 372 people aged > 60 years without dementia at recruitment . Main outcome measures Anticholinergic burden from drug use , cognitive examination , and neurological assessment . Results 9.2 % of subjects continuously used anticholinergic drugs during the year before cognitive assessment . Compared with non-users , they had poorer performance on reaction time , attention , delayed non-verbal memory , narrative recall , visuospatial construction , and language tasks but not on tasks of reasoning , immediate and delayed recall of wordlists , and implicit memory . Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35 % of non-users , and anticholinergic drug use was a strong predictor of mild cognitive impairment ( odds ratio 5.12 , P = 0.001 ) . No difference was found between users and non-users in risk of developing dementia at follow-up after eight years . Conclusions Elderly people taking anticholinergic drugs  had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired , although not at increased risk for dementia . Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors BACKGROUND Observational studies report a relationship between anticholinergic drug scale ( ADS ) score and cognitive function . This study investigated whether a reduced ADS score improved cognitive function in a frail elderly population . METHODS This r and omized , controlled , single-blinded trial , recruited long-term residents with an ADS score of greater than or equal to 3 from 22 nursing homes in Norway . The participants were r and omly allocated ( 1:1 ) to intervention or control . The intervention was a pharmacist-initiated reduction of ADS score after multidisciplinary drug review s. Primary end point was Consortium to Establish a Registry for Alzheimer 's Disease 10-wordlist test for immediate recall . Secondary end points were Mini-Mental Sate Examination , delayed recall and recognition of words , saliva flow , and serum anticholinergic activity (SAA).The participants were retested after 4 and 8 weeks , and the study groups were compared after adjusting for baseline differences . RESULTS Eighty-seven patients were included . The median ADS score was reduced by 2 units ( p < .0001 ) in the intervention group and remained unchanged in the control group . After 8 weeks , the adjusted mean difference in immediate recall was 0.54 words between the intervention and control group ( 95 % confidence interval [ CI ] : -0.91 , 2.05 ; p = .48 ) . The study groups did not differ significantly in any of the other cognitive end points , salvia flow , or SAA at either follow-up ( p > .18 ) . CONCLUSION Pharmacist-initiated drug changes significantly reduced ADS score but did not improve cognitive function  in nursing home residents . Moreover , the drug changes did not reduce SAA or mouth dryness significantly , which might indicate limited applicability of the ADS score to prevent prescription risks in this population Estrogen has been shown to interact with the cholinergic system and influence cognition in animal models . This study investigated the interaction of estrogen and cholinergic system functioning and the effects of this interaction on cognitive task performance in healthy older women . Fifteen post-menopausal women were r and omly and blindly placed on 1 mg of 17-β estradiol or placebo for 3 months after which they participated in five anticholinergic challenge sessions , where they were administered one of two doses of the antimuscarinic drug scopolamine ( SCOP ) or the antinicotinic drug mecamylamine ( MECA ) or placebo . After the first challenge phase , they were crossed over to the other hormone treatment for another 3 months and repeated the challenges . Performance in multiple domains of cognition was assessed during anticholinergic drug challenge , including attention and verbal and nonverbal learning and memory . Results showed that estrogen pretreatment attenuated the anticholinergic drug-induced impairments on tests of attention and tasks with speed components . This study is the first to demonstrate the interaction of estrogen and the cholinergic system and the effects on cognitive performance in humans . The results suggest that estrogen status may affect cholinergic system tone and may be important for cholinergic system integrity Background : Despite much being written on the topic , there are few surveys investigating the prevalence of anticholinergic adverse effects of antipsychotic drugs . One study , however , used trial-derived data to calculate estimates . Objectives : To investigate the prevalence/incidence rates of anticholinergic effects as viewed from within relevant r and omized trials . Methods : Data were extracted from each relevant study included in Cochrane review s. Data were checked , extracted , and simple frequencies , and 95 % confidence intervals ( CIs ) were calculated . Results : Many trials in relevant review s reported no data on anticholinergic effects ( estimate 40,000 participants ) . However , data were extracted from 177 studies within 54 review s ( N = 27,328 participants ) . Most data are short-term ( < 12 weeks ) . For blurred vision , the newer generations of drugs have rates of between 10 % and 20 % ( eg , risperidone , n = 1460 , 6 r and omized controlled trials [ RCTs ] , 11.9 % prevalence ; CI , 10 - 14 ; olanzapine , n = 1584 ; 4 RCTs , 12.2 % prevalence ; CI , 11 - 14 ) . These estimates are similar to those of sulpiride ( n = 186 ; 2 RCTs , 12.4 % ; CI , 8 - 18 ) and chlorpromazine ( n = 294 ; 10 RCTs , 11.2 % ; CI , 8 - 15 ) , less than trifluoperazine ( n = 167 ; 8 RCTs , 31.1 % ; CI , 25 - 39 ) , but considerably more than perphenazine ( n = 410 ; 8 RCTs , 3.7 % ; CI , 2 - 6 ) . Data are presented on a range of anticholinergic effects across different periods . Conclusions : Anticholinergic symptoms are common adverse effects associated with the use of all antipsychotic drugs , and newer-generation drugs are not clearly distinguishable from many older compounds . Adverse effect data should be more accessible BACKGROUND The use of drugs with anticholinergic adverse effects is often deemed inappropriate in elderly ( aged > or = 65 years ) patients , yet studies continue to show extensive use in this population at high risk for adverse drug events ( ADEs ) . The burden of drug-related anticholinergic symptoms in community-dwelling elderly patients has not been well described . OBJECTIVE The aim of this study was to assess the prevalence of anticholinergic symptoms , corresponding symptom burden , and anticholinergic-related ADEs in a sample of community-dwelling elderly veterans . METHODS This prospect i ve cohort study was conducted at the primary care clinics at the Veterans Affairs Medical Center ( VAMC ) , Iowa City , Iowa . The study sample included r and omly selected patients with intact cognitive function attending the VAMC and prescribed > or = 5 scheduled medications . Data on current prescription and nonprescription drug use were elicited by a trained research assistant and a clinical pharmacist from patient interviews and electronic medical records . The prevalence and severity of 7 anticholinergic symptoms ( dry mouth , constipation , blurred vision , confusion , urinary hesitation , dry eyes , and drowsiness ) were assessed at baseline . The occurrence of ADEs at 12 weeks was compared between patients using anticholinergic drugs and those not using them . RESULTS A total of 532 patients were included ( 97.9 % men ; mean age , 74.3 years ; 27.1 % used at least 1 anticholinergic drug )  . Twenty-two anticholinergic drugs ( 16 prescription medications , 6 over-the-counter medications ) were identified . The mean number of anticholinergic symptoms was significantly higher in the group using anticholinergic drugs ( 3.1 vs 2.5 ; P < 0.01 ) . However , only 2 symptoms were statistically more prevalent in the group using anticholinergic drugs : dry mouth ( 57.6 % vs 45.6 % ) and constipation ( 42.4 % vs 29.4 % ) ( both , P < 0.01 ) . At 12 weeks , only 1 ( 0.8 % ) patient in the group using anticholinergic drugs reported an ADE considered related to an anticholinergic drug . CONCLUSIONS Anticholinergic drug use was common ( 27.1 % ) in these elderly veterans with intact cognitive function . The mean number of anticholinergic symptoms was significantly greater in this group , and the prevalences of dry mouth and constipation were significantly higher in the group using anticholinergic drugs ( all , P < 0.01 ) . Anticholinergic-related ADEs were rare ( 0.8 % ) . Although anticholinergic drugs should generally be avoided in the elderly , individual risks and benefits for a patient should be considered Although there is an underst and able emphasis on the side effects of individual medications , the cumulative effects of medications have received little attention in palliative care prescribing . Anticholinergic load reflects a cumulative effect of medications that may account for several symptoms and adverse health outcomes frequently encountered in palliative care . A secondary analysis of 304 participants in a r and omised controlled trial had their cholinergic load calculated using the Clinician-Rated Anticholinergic Scale ( modified version ) longitudinally as death approached from medication data collected prospect ively by study nurses on each visit . Mean time from referral to death was 107 days , and mean 4.8 visits were conducted in which data were collected . Relationships to key factors were explored . Data showed that  anticholinergic load rose as death approached because of increasing use of medications for symptom control . Symptoms significantly associated with increasing anticholinergic load included dry mouth and difficulty concentrating ( P < 0.05 ) . There were also significant associations with increasing anticholinergic load and decreasing functional status ( Australia-modified Karnofsky Performance Scale ; and quality of life ( P < 0.05 ) . This study has documented in detail the longitudinal anticholinergic load associated with medications used in a palliative care population between referral and death , demonstrating the biggest contributor to anticholinergic load in a palliative care population is from symptom-specific medications , which increased as death approached 1 . Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients . 2 . Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism , we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement . 3 . Results were negative , since ( a ) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo ; ( b ) the number of intrusions tended to increase , rather than to decrease , after the treatment period We studied 16 patients with long-st and ing irritable bowel syndrome of moderate severity using a controlled , double-blind crossover method . Five sedative-anticholinergic drug combinations and a placebo were tested . The subjective response was assessed with four subjective methods to include an increasing number of response variables . The patients preferred 30 mg phenobarbital plus 8 mg belladonna ( P & B ) to placebo ( P = 0.02 ) . Five of ten patients were helped " some " or " a lot " with placebo , while ten of 15 were helped " some " or " a lot " with P & B ( P = 0.07 ) . The ten prominent-symptoms method revealed that subjective symptoms such as nervousness , sleep difficulties , and tiredness were experienced as greater problems than diarrhea . The factor analysis method documented a strong placebo response . Simpler evaluation methods such as drug preference and a five-choice method appear more likely to show a positive drug effect , while the inclusion of a larger number of variables appears to emphasize the placebo portion of the response . These observations may help explain some of the apparent discrepancies between the conclusions of some controlled clinical trials and subsequent clinical experience OBJECTIVES To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors ( ChIs ) and the bladder anticholinergics oxybutynin or tolterodine . DESIGN Prospect i ve cohort study . SETTING Nursing homes ( NHs ) in the state of Indiana . PARTICIPANTS Three thous and five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1 , 2003 , and December 31 , 2004 . Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine .  MEASUREMENTS Indiana Medicaid cl aims data were merged with data from the Minimum Data Set ( MDS ) . Repeated- measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale ( MDS-COGS ; scored 0 - 10 ) and change in activity of daily living ( ADL ) function using the seven ADL items in the MDS ( scored 0 - 28 ) . Potential covariates included age , sex , race , number of medications , and Charlson Comorbidity Index score . RESULTS Three hundred seventy-six ( 10.6 % ) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function , ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics ( ChI alone ) , compared with 1.62 points per quarter when taking dual therapy , a 50 % greater rate in quarterly decline in ADL function ( P=.01 ) . There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning . CONCLUSION In higher-functioning NH residents , dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone . The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts . There are few studies in cough due to natural disease especially using objective techniques . This paper presents data from a series of r and omized , double blind , placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections . In these studies , cough was quantified using a st and ardized and vali date d computerized system for the acquisition and multidimensional analysis of the cough sound . Key objective parameters like cough counts , intensity , latency and total effort expended were studied . Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease . Differences were observed in speed of action , and objective and subjective measures , that probably indicate differences in drug action . More recently , three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections . Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts , latency and total effort . These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments
medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function , but limited evidence exists for delirium or mortality outcomes
OBJECTIVES to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes .