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
|