Study Authors/Design Study Population Study Objective Drug Measure Adverse Event
Myint et al10 Cohort Study
25,639 men and women 40-79 years old from general practice registers in the EPIC-Norfolk cohort, UK followed for >10 years
To examine the relationships between total anticholinergic burden, all-cause mortality, and cardiovascular disease
Total Anticholinergic Burden Score using an Anticholinergic Burden Scale
Higher rates of all-cause mortality and cardiovascular disease in group with higher anticholinergic burden score
Hilmer et al6 Cohort Study
3,075 community-dwelling Medicare recipients aged 70-79 years, recruited from April 1997 to June 1998 in eastern USA
To determine if total drug burden exposure over 5 years is associated with reduced functional capacity at year 6
Drug Burden Index (DBI) (calculated based on anticholinergic agents and sedative use)
Higher DBI at years 1, 3 and 5 was consistently associated with poorer function at year 6; with a reduction in gait speed and grip strength
Chew et al132 Cohort Study
35 inpatients in a geriatric inpatient ward between February 2000 and April 2002 with behavioural and psychological symptoms of dementia (BPSD)
To examine association between serum anticholinergic activity (SAA) and cognitive performance in patients with moderate-to-severe dementia
SAA as measured by a radioreceptor competitive binding assay
Moderate negative correlation between SAA and Mini-Mental State Examination (MMSE) score
Golinger et al12 Cohort Study 25 patients in the surgical intensive care unit over a 3-month period
To determine presence of delirium and to estimate risk of delirium using SAA
Assay for SAA was performed on each sample by a radioreceptor method
The mean SAA was significantly higher for the delirious (4.67±3.3 ng/mL), versus non-delirious (0.81±1.0 ng/mL) patients
Study Authors/Design Study Population Study Objective Drug Measure Adverse Event/Outcome
Mulsant et al13 Cohort Study
201 randomly selected from a cohort of English-speaking adults ≥65 years who had serum samples collected between March 1995 and September 1997
To examine the relationship between SAA and cognitive performance in a cohort of community dwelling individuals
SAA as measured by a radioreceptor method
SAA was strongly associated with cognitive impairment and those participants with SAA higher than the 90th percentile were 13 times more likely to have an MMSE score below the 10th percentile than participants with an undetectable SAA
Han et al5 Cohort Study
Inpatients ≥65 years of age with delirium, admitted to medical or geriatric services
To evaluate the association between use of anticholinergic medications and severity of delirium
Anticholinergic medication use calculated by: Summer’s Drug Risk Number Clinician-rated anticholinergic score Number of anticholinergic medications Number of non-anticholinergic medications Total number of medications
Increase in delirium severity was significantly associated with the clinician-rated anticholinergic score and the number of anticholinergic medications for both those with and without baseline dementia
Study Authors/Design Study Population Study Objective Drug Measure Adverse Event/Outcome
Haab et al133 Noncomparative, open-label study 719 adults (85.1% women), mean age 57.3 years, with 29.9% aged ≥65 years who had completed a feeder darifenacin study
The primary objective was to assess the long-term safety, tolerability and efficacy of darifenacin in patients with overactive bladder
Darifenacin controlled release 7.5 or 15 mg orally once daily
The most commonly reported adverse events were dry mouth and constipation, for which the all-causality incidence was 23.3% and 20.9%, respectively with 0.4% of patients reporting hypertonia, somnolence and paresthesia
Ancelin et al3 Cohort Study 372 elderly participants without dementia aged >60 years randomly selected from 63 general practitioners in the Montpellier region of southern France
To assess the potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment in elderly people
From an extensive literature review a table was created associating known anticholinergic drugs with their SAA and participant’s records were examined to classify the anticholinergic burden from 0 to 3
Anticholinergic drug users had poorer simple reaction time, attention, immediate and delayed visuospatial memory, narrative recall, verbal fluency, object naming, and visuospatial construction and anticholinergic drug use was a significant predictor of mild cognitive impairment (OR 5.12; 95% CI[1.94 to 13.51])
Study Authors/Design Study Population Study Objective Drug Measure Adverse Event/Outcome
Lechevallier-Michel et al9 Cross-sectional Study
3,777 subjects among French elderly ≥65 years, living in the community in two administrative areas in south western France
The aim of this study was to assess the association between the use of drugs with anticholinergic properties and cognitive performance among community-dwelling elderly subjects Anticholinergic drugs from seven therapeutic classes were examined: antihistamines, gastrointestinal and urinary antispasmodics, antiemetics, bronchodilators, antiparkinsonian drugs, antidepressants and antipsychotics Current use of anticholinergic drugs was significantly associated with low cognitive performance on cognitive tests (MMSE, BVRT, IST) among community- dwelling elderly people
Geller et al134 Cohort Study
50 cognitively intact women aged ≥55 years seeking treatment for overactive bladder
To investigate the effect of trospium chloride extended release, on cognitive function in postmenopausal women in a clinic setting
Hopkins Verbal Learning Test (HVLT-R) assessed at day 1, at week 1, 4 and 12 of treatment with trospium chloride
At week 1 there was a decline in the HVLT-R learning subscale (p=0.029), at week 4 the HVLT-R Total Recall subscale score was improved over baseline (p=0.02)
Hill et al135 Noncomparative, open-label study 716 patients aged ≥65 years with overactive bladder who had first completed 12 weeks of a feeder study
To determine the long-term safety, tolerability and efficacy of darifenacin in patients ≥65 years of age
darifenacin 7.5 mg once daily for 2 weeks then a dose increase to 15 mg once daily with monitoring of safety, tolerability and efficacy
Dry mouth and constipation led to discontinuation in 2.3 and 4.2% of participants respectively, cardiovascular and peripheral/CNS adverse events were infrequently reported; 1.4% and 3.3% respectively
Study Authors/Design Study Population Study Objective Drug Measure Adverse Event/Outcome
Armstrong et al136 Pooled data from 2 multicenter, randomized, double-blind, parallel group trials
1,168 patients ≥18 years of age with a diagnosis of overactive bladder, as defined by urge urinary incontinence, urgency and frequency
To describe the safety and tolerability of extended-release oxybutynin at 10 mg once daily and to compare the safety profile with that of tolterodine 4 mg once daily
Extended-release oxybutynin 10 mg once daily, immediate-release tolterodine 2 mg twice daily and extended-release tolterodine 4 mg once daily were compared over 12 weeks
Approximately 10% of participants had one or more adverse events associated with the nervous system, with no clinically relevant differences across the three treatment groups (extended-release oxybutynin, 10.2%; extended-release tolterodine, 8.3%; and immediate release tolterodine, 10.9%)
Koyama et al8 Cohort Study
4,606 women ≥65 years of age recruited in Minneapolis, Minnesota; Portland, Oregon; Baltimore, Maryland; or Monongahela Valley, Pennsylvania between 1986 and 1988
To determine whether anticholinergic load is associated with a higher risk of functional impairment and low cognitive performance
Anticholinergic load measured using the total score on the Anticholinergic Cognitive Burden scale (ACB)
A one-unit increase in ACB score was significantly associated with one or more new Instrumental Activities of Daily Living (IADL) impairments (OR 1.11; 95% CI [1.04 to 1.19]) and with worse cognitive performance
Study Authors/Design Study Population Study Objective Drug Measure Adverse Event/Outcome
Fox et al4 Longitudinal Study
13,004 participants representative of the population aged ≥65 living at home or in institutions in England and Wales
To identify if the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and death in older people Each participant’s anticholinergic burden was calculated using the ACB
A dose-response relationship was observed between increased total ACB score and MMSE decline, with a score of 4 or more on the ACB associated with a 0.34 (95% CI [0.01 to 0.67]) lower MMSE score than those not taking anticholinergics and for each 1 point increase in ACB, the odds of dying increased by 26% (OR 1.26; 95% CI [1.20 to 1.32])
Kalisch Ellett et al7 Cohort Study
36,015 subjects from the Australian veteran community, which includes veterans and war widows and widowers with median age 80
To examine the effect of use of anticholinergic medications on the risk of hospitalization for confusion, dementia, or delirium
The estimated daily number of anticholinergic medications were expressed as no medication or one, two, three or more anticholinergic medications The risk of hospitalization was greater when using two (RR 2.58; 95% CI [1.91 to 3.48]), or three or more anticholinergic medications (RR 3.87; 95% CI [1.83 to 8.21]) than when participants were not exposed to anticholinergic medications