BMJ: Use
of certain anticholinergic drugs - that help to control involuntary
muscle movements for conditions such as Parkinson’s disease - is
associated with an increased risk of dementia, finds a UK study
published by The BMJ today. The
study is the largest of its kind to date and the findings prompt the
researchers to say that clinicians should avoid long term prescribing of
some anticholinergics to patients aged 45 and over.
Anticholinergic
drugs block chemical signals to the brain that control muscle
movements. They are often used for conditions linked to involuntary
muscle movements, such as urinary incontinence and Parkinson’s disease,
as well as for depression, chronic lung disease (COPD) and asthma.
Several
studies have reported associations between use of anticholinergics and
future cognitive decline and dementia, but it is not clear whether this
is due to the drugs themselves or the underlying conditions for which
they were prescribed.
So
a research team led by George Savva at the University of East Anglia,
set out to estimate the association between duration and level of
exposure to different classes of anticholinergic drugs and subsequent
dementia.
They
analysed data from the UK’s Clinical Practice Research Database for
40,770 patients aged 65 to 99 years who were diagnosed with dementia
between April 2006 and July 2015. Each case patient was matched to up to
seven control patients of similar age and sex, but without dementia.
Drugs
were scored according to their anticholinergic activity using the
Anticholinergic Cognitive Burden (ACB) scale. An ACB score of 1 was
classed as possibly anticholinergic, while a score of 2 or 3 was
definitely anticholinergic.
Daily
doses of each drug were then compared for both cases and controls over
an exposure period of 4 to 20 years before a diagnosis of dementia.
A
total of 14,453 (35%) cases and 86,403 (30%) controls were prescribed
at least one anticholinergic drug with an ACB score of 3 during this
period.
After
taking account of potentially influential factors, the researchers
found that definite anticholinergic antidepressants, antiparkinson
drugs, and drugs to treat urinary incontinence (ABC score of 3) were
linked to increased dementia risk up to 20 years after exposure.
However,
no increased risk was found for drugs with possible anticholinergic
activity (ACB score of 1) - and for anticholinergic gastrointestinal or
respiratory drugs (ACB score of 3).
Other
antidepressants (mainly selective serotonin reuptake inhibitors) with
an ACB score of 1 were linked to dementia, but only close to the time of
prescription, which the researchers say is unlikely to represent a
direct (causal) link.
This
is an observational study, so no firm conclusions can be drawn about
cause and effect, and the authors outline some limitations, such as
possible misclassification of dementia cases and a lack of information
on depression severity. Nevertheless, the study was large and was able
to account for several potentially influential factors.
They
suggest that the association “could be caused by a class specific
effect, or by drugs being used for very early symptoms of dementia” and
they call for further research into the effects of specific drug
classes.
In
the meantime, they say clinicians “should continue to be vigilant with
respect to the use of anticholinergic drugs, and should consider the
risk of long term cognitive effects, as well as short term effects,
associated with specific drug classes when performing their risk-benefit
analysis.”
In
a linked editorial, Professor Shelly Gray at the University of
Washington and Professor Joseph Hanlon at the University of Pittsburgh,
say this research “raises important issues about the best way to
summarise anticholinergic burden for future research.”
In
the meantime, they agree that anticholinergics in general should be
avoided in older adults. “Specifically, for most highly anticholinergic
drugs, non-pharmacological and pharmacological alternatives are
available and should be considered,” they conclude.
[Ends]
Research: Anticholinergic drugs and risk of dementia: case-control study
https://www.bmj.com/content/361/bmj.k1315
https://www.bmj.com/content/361/bmj.k1315
Editorial: Anticholinergic drugs and dementia in older adults
https://www.bmj.com/content/
https://www.bmj.com/content/
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