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com
Research paper
< See Editorial Commentary,
p129
1
Department of Psychiatry,
Stavanger University Hospital,
Stavanger, Norway 2The
Norwegian Centre for
Movement Disorders, Stavanger
University Hospital, Norway
3
Department of Neurology,
Stavanger University Hospital,
Stavanger, Norway 4Federal
Institute for Drugs and Medical
Devices (BfArM), Bonn,
Germany 5Wolfson Center for
Age-Related Diseases, Kings
College, London, UK 6Institute of
Clinical Medicine, University of
Bergen, Bergen, Norway
Correspondence to
Dr Uwe Ehrt, Stavanger
University Hospital, Psychiatric
Clinic, PO Box 1163, Hillevåg,
4095 Stavanger, Norway;
uehr@sus.no
CB has received honoraria from
Novartis, Pfizer, Shire, Lundbeck,
Myriad, Janssen, Astra Zeneca
and Servier pharmaceutical
companies, and research grants
from Novartis, Lundbeck,
Astra-Zeneca and Janssen
pharmaceuticals. DA has
received honoraria from
Novartis, Lundbeck, GE Health
and Merck Serono and received
9.5 mill NOK, 2003e2007 (Age
Research programme 153480);
Health Region Western Norway;
500 000 NOK/year, 2008e2010
for the project Neurochemistry
for dementia and PD;
unrestricted industry grants
100 000 NOK/year from Kavli
fund. DA received honoraria
from Novartis, Lundbeck, GE
Health and Merck Serono.
Received 1 July 2009
Revised 17 August 2009
Accepted 21 August 2009
Published Online First
21 September 2009
160
Use of drugs with anticholinergic effect and impact on
cognition in Parkinson’s disease: a cohort study
Uwe Ehrt,1 Karl Broich,4 Jan Petter Larsen,2,3 Clive Ballard,5 Dag Aarsland1,6
ABSTRACT
Background Cognitive decline is common in Parkinson’s
disease (PD). Although some of the aetiological factors
are known, it is not yet known whether drugs with
anticholinergic activity (AA) contribute to this cognitive
decline. Such knowledge would provide opportunities to
prevent acceleration of cognitive decline in PD.
Objective To study whether the use of agents with
anticholinergic properties is an independent risk factor for
cognitive decline in patients with PD.
Methods A community-based cohort of patients with PD
(n¼235) were included and assessed at baseline. They
were reassessed 4 and 8 years later. Cognition was
assessed using the Mini-Mental State Examination
(MMSE). A detailed assessment of the AA of all drugs
prescribed was made, and AA was classified according to
a standardised scale. Relationships between cognitive
decline and AA load and duration of treatment were
assessed using bivariate and multivariate statistical
analyses.
Results More than 40% used drugs with AA at baseline.
During the 8-year follow-up, the cognitive decline was
higher in those who had been taking AA drugs (median
decline on MMSE 6.5 points) compared with those who
had not taken such drugs (median decline 1 point;
p¼0.025). In linear regression analyses adjusting for age,
baseline cognition and depression, significant
associations with decline on MMSE were found for total
AA load (standardised b¼0.229, p¼0.04) as well as the
duration of using AA drugs (standardised b 0.231,
p¼0.032).
Conclusion Our findings suggest that there is an
association between anticholinergic drug use and
cognitive decline in PD. This may provide an important
opportunity for clinicians to avoid increasing progression
of cognitive decline by avoiding drugs with AA. Increased
awareness by clinicians is required about the classes of
drugs that have anticholinergic properties.
INTRODUCTION
Cognitive impairment and dementia are frequent in
Parkinson’s disease (PD)1 with major consequences
for daily functioning, quality of life, care giver
burden and health-related costs. Cortical Lewy
bodies, diffuse a-synuclein aggregates, Alzheimer-
type changes including amyloid plaques and
neurofibrillar tangles, and neurochemical changes all
contribute to dementia in PD. Of the cortical
neurochemical alterations, cholinergic deficits
appear to be particularly important, and are
associated with cognitive impairment in both
postmortem2 and in vivo3 studies.
J Neurol Neurosurg Psychiatry 2010;81:160e165. doi:10.1136/jnnp.2009.186239
There is increasing awareness in a variety of
conditions that certain drugs may accelerate
cognitive decline. For example, drugs with anti-
cholinergic properties are widely used and may
cause central nervous system anticholinergic syn-
dromes like delirium and cognitive impairment.4e6
Because of the increased permeability of the
bloodebrain barrier, age-related pharmacodynamic
changes, the risk for polypharmacy and interac-
tions, the ageing brain is particularly sensitive to
these toxic effects.7 8
Although the prescription of anticholinergic
agents as a treatment for the motor symptoms of
PD is now less favoured, it is not at all uncommon
that patients with PD receive drugs with anticho-
linergic properties. Some agents targeting motor
and bladder symptoms, and drugs used to treat
common neuropsychiatric symptoms including
depression9 and psychosis,10 have anticholinergic
properties. Comorbid physical conditions are also
common in elderly PD patients, and many drugs
commonly prescribed for older people such as
bronchodilatators, antiarrhytmic drugs, corticoste-
roids, analgesics, antihistamines or antihyperten-
sives have also anticholinergic properties, many of
which are not recognised as anticholinergics by
a substantial proportion of physicians.5 7 8
Patients with brain diseases with cholinergic
deficits are particularly sensitive to anticholinergic
drug-effects. For example, drugs with anticholin-
ergic effects were found to be significantly associ-
ated with a higher risk in women to progress from
mild cognitive impairment to dementia.11 In
another study, antipsychotic drugs were associated
with worsening cognitive decline in people with
dementia, potentially due to their anticholinergic
activity (AA).12 In a direct comparison of two
antipsychotic agents with and without AA, the
increase in AA measured with radioreceptor
assay was found in the group taking the drug
with AA, and this increase was associated with
increase in anticholinergic side effects and cognitive
slowing.13
Given the reduced cholinergic function in PD and
its association with cognitive impairment, drugs
with anticholinergic activities may contribute to
the observed cognitive impairment in people with
PD. However, this hypothesis has not been
systematically investigated. Therefore, using data
from a prospective, longitudinal study, the use and
impact of drugs with anticholinergic properties in
a community-based sample of patients with PD
was studied. Such information is important for the
management of patients with PD, as avoiding
drugs which accelerate cognitive decline may be
a key part of optimal therapy.
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MATERIAL AND METHODS
Patients: longitudinal community cohort of PD patients
Patients were drawn from a longitudinal prospective commu-
nity-based prevalence study of 245 patients diagnosed as having
PD on 1 January 2003 in Rogaland County, Norway. Three
patients were rediagnosed as not having PD during follow-up,
and seven had insufficient data about their medication or MMSE
score, leaving 235 patients for this study. The recruitment
strategy, patient samples, and design of this study have been
described elsewhere.14 PD was diagnosed according to published
criteria15 by neurologists with special expertise in movement
disorders. Patients with dementia, diagnosed according to DSM
IIIR as previously described,16 were included if it was clearly
established that onset of dementia occurred at least 1 year after
onset of PD. Twenty-seven of the total PD population have come
to autopsy, and the diagnosis of PD was confirmed neuro-
pathologically in all cases.16 After a comprehensive baseline
assessment, patients were followed longitudinally and reassessed
after 4 and 8 years, including a full drug history. A total of 146
subjects were available at 4-year and 92 at 8-year follow-up
evaluation. Attrition was mainly due to death; only 14 (year 4)
and five (year 8) subjects refused to participate or could not be
traced (figure 1). Information on the assessment at follow-up has
been provided elsewhere.17
BASELINE ASSESSMENT
Clinical assessment at baseline
Cognition was assessed with the Mini-Mental State Examina-
tion (MMSE)18 at baseline and at each follow-up assessment.
The clinical examination of motor symptoms included disease
stage according to the Hoehn and Yahr Scale.19 Depression was
rated using a clinical rating scale, the MontgomeryeÅsberg
Depression Rating Scale (MADRS), by a neurologist after
a training procedure.20 Major depression according to DSM IIIR
was diagnosed after a clinical interview as previously described.14
Follow-up assessments were completed with the same instru-
ments at 4- and 8-year visits as part of a systematic longitudinal
follow-up of the cohort.
Measurement of anticholinergic load
To estimate the use of with AA in our sample, we modulated the
procedures recommended by Chew et al.5 In that study, the AA
of 107 medications commonly prescribed to older adults was
Figure 1 Flow chart showing the distribution of
patients and use of drugs with anticholinergic activity at
the three assessment points.
J Neurol Neurosurg Psychiatry 2010;81:160e165. doi:10.1136/jnnp.2009.186239
Research paper
detected using an in vivo radioreceptor assay, grading them in five
levels, 0 (no AA); 0/+ (no or minimal AA), + (low AA), ++
(moderate AA) and +++ (high AA). We transformed this grad-
uation in five categorical scores from 0 to 4. For drugs which were
not included in this study, AA scores were specified by two of the
authors independently from each other using available evidence
from the literature (UE and KB). The scores from every agent
used by each patient were summed up, and this sum score was
considered as the total AA load. This was done for each assess-
ment point. For the 8-year observation period, a total AA load
was calculated by adding together the AA load at baseline and the
two follow-up assessments.
The scale does not take into account the individual doses of
the drugs. Furthermore, there was no detailed information
available for the start and stop date of the drugs. Therefore, to
estimate the duration of treatment with AA drugs, the number
of assessment points with AA drugs was calculated, that is, each
patient would have a duration category between 0 (never) and 3
(at each assessment).
Analyses
Statistical analyses were performed using the software program
SPSS V.16 (SPSS, Chicago). To examine if patients who received
AA drugs differed from those who did not on demographic and
clinical variables at baseline, comparisons of normally distrib-
uted continuous variables were carried out using a one-way
analysis of variance. The ManneWhitney U test was used for
non-normally distributed variables. The c2 test was used for
categorical variables. The primary outcome variable was the rate
of cognitive decline, that is, the difference between MMSE scores
at baseline MMSE and at 8-year follow-up. A secondary confir-
mative analysis was undertaken, focusing on the baseline
cognitive performance. Normality was assessed using the
KolmogoroveSmirnov test. Only patients with follow-up data
on MMSE were included.
Multivariate hierarchical linear regression analyses were
performed to adjust for potential confounders, with cognition or
change in cognition as dependent variable, and AA load or AA
duration as predictor. In the first model, age, education and
gender were entered, then baseline MMSE and MADRS scores,
and finally the AA drug use.
p Values less than 0.05 were considered statistically
significant.
161
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Research paper

RESULTS was 9.2 (5.8) years. The median (interquartile range (IQR))
Cross-sectional analyses Hoehn & Yahr Score was 3,2 MADRS 69 and MMSE 27.6
Of the 235 patients included at baseline, 114 (48.5%) were men, A total of 99 substances were used by the PD patients, and 29
the mean (SD) age was 74.7 (8.4) years, and the duration of PD of these drugs had clinically relevant AA. The AA rating of all the

Table 1 Rating of anticholinergic activity of drugs used in the sample

Drug class 0 1 2 3 4
Antiparkinsonian agents Bromocriptin Benztropine
Cabergoline Orphenadrine
Levodopa Trihexyphenidyl
Ropinirole
Pergolide
Pramipexole
Selegilin
Tolcapone
Analgetics and anti-inflammatory Acetylsalicylic acid Propoxyphene
drugs Buprenorphine
Codeine
Ibuprofen
Ketoprofen
Naproxen
Paracetamol
Pentazocine
Pethidine
Piroxicam
Sulindac
Antidepressants Mianserin Citaloprame Nortryptyline Amitriptyline
Moclobemid Fluoxetine Paroxetine Doxepine
Sertraline Fluvoxamine Trimipramine
Venlafaxine
Antipsychotics Chlorprotixen Quetiapine Promazine Clozapine
Haloperidol Olanzapine Thioridazine
Melperone
Perphenazine
Prochlorperazine
Antidiabetic agents Glibenclamide
Glipizide
Anxiolytics and sedative drugs Clomethiazole Diazepame
Nitrazepam Flunitrazepame
Oxazepam Phenobarbital
Zopiclone
Cardiovascular agents Amlodipin Digitoxin
Atenolol Digoxin
Bumetamide furosemide
Hydrochlorothiazide
Captopril
Disopyramid
Dipyridamol
Enalapril
Isosorbiddinitrat
Lisinopril
Nifedipin
Nitroglycerin
Timolol
Verapamil
Miscellaneous Alimemazin, Lansoprazole Ranitidine Emepronium
Allopurinol, Theophylline Oxybutinine
Atorvastatin, Ipratropium
Carbamazepin
Chlorambucil
Dimeticone
Donepezil
Estriol
Galantamin
Insulin
Losartan
Metoclopramid
Metoprolol
Omeprazole
Prednisolon
Salbutamol
Simvastatin
Spironolactone
Tamoxifen
Terbutalin
Thyroxin
Warfarin

162 J Neurol Neurosurg Psychiatry 2010;81:160e165. doi:10.1136/jnnp.2009.186239

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Table 2 Demographic and clinical characteristics of Parkinson’s disease (PD) patients at baseline
Statistics
PD patients receiving
PD patients not receiving agents with AA Degree(s) p
Baseline characteristic agents with AA n[133 n[102 Test of freedom Value
Female n (%) 66 (49.6) 55 (53.9) Pearson c2¼0.427 1 0.301
Age (years) 74.2 (9.07) 75.28 (7.34) ANOVA; F¼2.561 1; 233 0.105
Duration of PD (years) 8.32 (5.41) 10.62 (6.04) ANOVA; F¼0.724 1; 233 0.396
Education (years) 9.5 (3.2) 8.7 (2.4) <0.05
MontgomeryeÅsberg depression rating scale score* 6 (5.25) 9 (9.25) <0.001
Major depression, n (%)y 5 (3.9) 13 (12.9) 0.013
Mini-Mental State Examination score* (range) 28 (4) (0 to 30) 25 (7) (0 to 30) 0.001
Dementia n (%) 29 (21.0) 33 (32.4) 0.074
Hoehn & Yahr stage* 2.5 (1) 3 (1.5) 0.001
AA, anticholinergic activity; ANOVA, analysis of variance.
*Numbers represent mean (SD) or median (interquartile range) (ManneWhitney test).
yData available for 228 subjects.

used agents is displayed in table 1. At baseline, 102 of the 235 at some point during the study are shown in table 4 . The median
patients (43.4 %) received at least one drug with AA. The most (IQR) change in MMSE over the full 8-year period in subjects
common drugs with AA were antidepressants (n¼84), cardio- who had used AA drugs at some point (n¼56) was 6.5 points
vascular agents (n¼80), anxiolytics and sedatives (n¼61), and (IQR 15.3), whereas those who had not used AA drugs at any
antipsychotics (n¼44). Seventy-two subjects (30.6%) were assessment (n¼20) declined by only 1 point (IQR 6.25). This
taking more than one AA drug (total range 0e5). A total of 75 difference was significant (ManneWhitney test z¼2.5,
subjects (74.5%) took psychotropics: 17 patients (16.7%) received p¼0.025). The correlation between total AA load during the
antidepressants only, five (4.9%) an antipsychotic only, 12 8 years (ie, sum of AA load at all three assessments) and the
(11.8%) an anxiolytic only and 41 (40.2%) a combination of change in MMSE score was significant (Spearman r¼0.32,
psychotropic and other AA drugs. Cholinesterase inhibitors were p¼0.004). In the linear regression analysis, after adjustment for
used by only three patients during the study period. gender, education, age and baseline Hoehn & Yahr stage scores at
The baseline characteristics of patients receiving drugs with baseline, the association between AA load and MMSE decline
AA at baseline and those without drugs are shown in table 2. was significant and remained significant after including baseline
Patients taking AA agents had significantly lower cognition MMSE and MADRS scores (b 0.162, SE 0.077, standardised
(median 25) and higher depression scores9 than those not taking b¼0.229, p¼0.040; total model F¼3.1, p¼0.010). Similarly, there
AA agents (28 and 6, respectively), whereas age, duration of PD, was a significant association between duration of use of AA
or severity of motor symptoms did not differ significantly. Total drugs and cognitive decline after adjustment for age, education,
AA load correlated significantly with MMSE (Spearman gender, baseline Hoehn and Yahr stage, and baseline MMSE
r¼0.205, p¼0.002) and MADRS (Spearman r¼0.321, p<0.001). and MADRS scores in a multivariate linear regression analysis
Using linear regression analysis, after adjusting for age and (b¼1.8, SE 0.9, standardised b 0.231, p¼0.032, total model F¼4.9,
gender, MADRS (standardised b 0.291, p<0.001) but not MMSE p<0.001).
score remained significantly associated with the AA load in
a linear regression analysis. DISCUSSION
We report a significant association between drugs with AA and
Longitudinal analyses the rate of cognitive decline in a large and community-based
Seventy-six of the 92 patients seen at 8-year follow-up cohort of patients with PD followed prospectively for 8 years.
completed an MMSE. The characteristics of those completing The rate of decline was 6.5 times higher in the group using such
MMSE at follow-up and those who did not are shown in table 3. drugs compared with those never taking drugs. Our finding of an
The characteristics at follow-up of those who had used AA or not association between cognition and estimates of load and dura-
tion of AA drug use after adjustment for potential confounders
adds robustness to the findings and is consistent with studies in
Table 3 Demographic and clinical baseline characteristics of the general population. Emphasising the importance of the
Parkinson’s disease (PD) patients who did or did not complete 8 years’
follow-up
PD patients PD patients Table 4 Clinical characteristics of Parkinson’s disease (PD) patients at
completing not completing 8 years’ follow-up
follow-up follow-up p PD patients PD patients
Baseline characteristic (n[78) (n[157) Value not receiving receiving
Clinical feature at agents with agents with p
Female n (%) 42 (53.8) 79 (50.3) 0.6
8-year follow-up AA (n[20) AA (n[56) Value*
Age (years) 68.7 (8.4) 77.7 (6.5) 0.000
Duration of PD (years) 8.9 (4.8) 9.1 (6.2) 0.7 MontgomeryeÅsberg depression 5 (3.0) 8.5 (12.75) 0.31
rating scale score (n¼61)
Education (years) 9.6 (3.3) 9.0 (2.8) 0.14
MMSE score 28 (9) 21 (16) 0.002
MontgomeryeÅsberg depression 6 (7) 7 (7) 0.16
rating scale score* MMSE decline 1 (6.75) 6.5 (15.25) 0.025
Mini-Mental State Examination score* 29 (3) 26 (8.3) 0.000 Dementia n (%) 6 (30.0) 36 (64.3) 0.013
Dementia n (%) 4 (5.1) 58 (36.9) 0.000 Hoehn & Yahr stage 2.5 (1) 3 (1.8) 0.000
Hoehn & Yahr stage* 2.5 (1.5) 3 (1.5) 0.000 All values are median (interquartile range).
AA, anticholinergic activity; MMSE, mini-mental state examination.
*Numbers represent median (interquartile range) (ManneWhitney test). *ManneWhitney U test.

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Research paper
finding to the population of people with PD, at baseline, more
than 40% used at least one drug with AA.
The additional finding of an association between AA drug use
and depression at baseline is in line with previous studies
reporting an association between cholinergic deficit in Lewy
body diseases with depression.3 However, although this associ-
ation remained significant after adjustment for age and gender, it
is possible that it is entirely due to antidepressant drugs being
given to patients with more severe depression. Similarly, an
uneven distribution of other psychopathologies, some of which
may be associated with cognitive impairment in PD, and
frequently treated with drugs with AA effects, might also have
influenced the findings. A recent trial with nortriptyline, a tricy-
clic antidepressant with AA, demonstrated superior efficacy over
placebo, with no worsening of cognition.25 Our findings,
however, suggest marked long-term cognitive effects of drugs
with AA which may offset the positive effect on mood. Clinical
judgement is required to solve this dilemma.
There are several potential mechanisms for a more rapid
decline in PD patients taking AA drugs. First, cholinergic activity
is reduced in PD.2 Cholinergic activity enhances attentional
processes and other cognitive functions,6 and drugs with anti-
cholinergic effects induce impairments in various cognitive
domains including memory22 and language.21 Stimulation of
cholinergic circuits seem to increase cerebral perfusion, and thus
cholinergic blockade may cause neurovascular dysregulation and
worsen cognition.26
In addition, there is convincing evidence linking muscarinic
receptor activity to the processing of amyloid precursor protein in
animal models, with stimulation of muscarinic receptors
increasing non-amyloidogenic processing.27 This might explain
the findings that drugs with anticholinergic effects were associ-
ated with more severe amyloid plaques,27 and conversely that
cholinergic drugs may reduce cortical amyloid load.28 There is
also evidence that activitation of muscarinic receptors may
prevent tau phosphorylation,24 which may explain the findings
of increased neurofibrillar tangles after anticholinergic treatment
in PD27 and neuroleptic treatment in dementia with Lewy
bodies.29 There is also preliminary evidence linking muscarinic
receptor activation to the processing of a-synuclein,30 the key
protein in the pathogenesis of PD and the main substrate under-
lying cognitive decline in PD.16 In addition, cholinergic deficits
have been reported to be associated with reduced neurogenesis.23
There are methodological limitations that need to be consid-
ered when interpreting these findings. First, due to the long
testeretest interval, there was a high attrition due to death, and
some of the survivors could not provide adequate scores on tests
such as MMSE and MADRS. Since dementia is associated with
mortality in PD, this may have introduced a selection bias. In
addition, the long interval increased the likelihood that changes
in drug treatment relevant to the study would go undetected.
Second, since this was a naturalistic study, and patients were not
randomised to AA treatment, the groups taking AA drugs may
have differed from those not taking such drugs. As discussed
above, it is possible that patients who were already on a steeper
trajectory of cognitive decline, due to coexisting psychopa-
thology or dementia, were more likely to be prescribed AA drugs.
However, there were no differences in the motor symptoms or
age at baseline. Depression was, however, more severe in those
with AA at baseline. This might have influenced the finding,
since depression has been found in some studies to be associated
with increased cognitive decline.31 However, we have not found
such an association in our longitudinal studies.17 This aspect is
further complicated by antidepressants being one of the most
164
commonly used AA drugs in this study. However, it is highly
unlikely, for ethical reasons, that randomised trials with drugs
with anticholinergic effects will be performed to clarify these
issues.
Since a relationship between cognitive impairment and drugs
with anticholinergic properties has been discussed for many
years based on findings in non-PD cohorts, clinicians might also
have reduced the anticholinergic load in patients with emerging
cognitive decline, which would have attenuated any relationship
between cognitive impairment and AA drugs. Finally, MMSE is
not a very sensitive measure of cognitive impairment in PD.32
This strengthens the finding of the observed association between
AA and cognitive impairment, and an even stronger association
might have been observed if more sensitive cognitive measure-
ments had been applied.
Strengths of the study include the large and community-based
cohort and the long, prospective follow-up period. Standardised
clinical assessments were performed, and the diagnosis of PD
was made by movement-disorder specialists, according to oper-
ationalised criteria. Patients were continually followed by
a study neurologist during the observation period, which
increases the accuracy of a clinical diagnosis of PD. In addition,
a subset of patients have come to autopsy with confirmation of
the diagnosis in all cases.16
A further strength is the detailed assessment of the anticho-
linergic load, taking into account both the duration and total
dosage, and including not only the well-known drugs such as
tricyclic antidepressants and neuroleptics, but also other drugs
associated with such effects. There is no universally accepted
method yet to assess and quantify the anticholinergic burden.
Older measures of anticholinergic medication exposure were
developed based on clinical experience and knowledge of the
pharmacological properties of the medications drawn from the
literature.33 34 Serum radioreceptor assay quantifying the drug
induced muscarinic blockade has been used to detect serum
AA.35 36 However, serum AA may reflect primarily the peripheral
endogenous and exogenous AA and may be less representative for
the anticholinergic effects on brain and cognition.37 We used
a recently published classification that takes into account the
dose-dependent anticholinergic properties of the drugs, since
higher doses than the clinically relevant doses may be required for
some drugs to induce anticholinergic effects.5 We slightly modi-
fied the scale by also including drugs which were not included
previously, after independent assessment by two of the authors.
A limitation with this method was that dosage and duration of
treatment are not taken into account.
In conclusion, we found that drugs with anticholinergic
properties are commonly administered to patients with PD, and
that the number and treatment treatment duration of drugs
with AA seem to be associated with more rapid cognitive
impairment. These findings have implications for the manage-
ment of PD patients, since avoiding such drugs may avoid
increasing progression of cognitive decline, and highlight the
need for continued physician education to ensure avoidance of
inadvertent prescription of such drugs.
Funding The study was funded by the Stavanger Hospital Trust, Norway. UE was
supported by a grant from Helse Vest, Norway. The funders had no role in the planning
of the study or interpretation of the results.
Competing interests None.
Ethics approval Ethics was approved by the Regional Committees for Medical and
Health Research Ethics (REK), Western Norway.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
J Neurol Neurosurg Psychiatry 2010;81:160e165. doi:10.1136/jnnp.2009.186239
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Use of drugs with anticholinergic effect and

impact on cognition in Parkinson's disease:
a cohort study
Uwe Ehrt, Karl Broich, Jan Petter Larsen, et al.

J Neurol Neurosurg Psychiatry 2010 81: 160-165 originally published

online September 21, 2009
doi: 10.1136/jnnp.2009.186239

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