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Anticholinergic drugs may be linked to increased risk of dementia

Doctors urged to avoid long-term prescribing of anticholinergic drugs to older patients

Ingrid Torjesen

Thursday, 26 April 2018

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, suggests a study* published by The BMJ.

Based on their findings, the researchers recommend that doctors 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 and so are often used to treat conditions linked to involuntary muscle movements, such as urinary incontinence and Parkinson’s disease, as well as for depression, chronic lung disease 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.

Researchers 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 in one of the largest studies to date.

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, and each case was matched with seven controls of similar age and sex.

The anticholinergic activity of drugs prescribed to each patient was scored 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 four to 20 years before a diagnosis of dementia, which revealed that 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, anti-Parkinson's 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.

The researchers 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 said 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.”

Commenting on the study, Professor Rob Howard, Professor of Old Age Psychiatry at UCL, said: “We already know that anticholinergic drugs can precipitate the presentation of people with early dementia, but this is the first convincing demonstration that the use of the drugs many years before dementia diagnosis might increase risk. The results are interesting but it is too early to conclude that use of these drugs ‘causes’ later dementia and people should talk to their doctors before stopping or changing of the medications implicated. It is possible that use of some of these drugs may have actually been to treat the very earliest symptoms of Alzheimer’s disease, which can be associated with low mood and lower urinary tract infections, many years before the development of dementia.”

Professor Stephen Evans, Professor of Pharmacoepidemiology at London School of Hygiene and Tropical Medicine, said: “The authors are very careful to note some of the limitations of the study, but some of their wording suggests that they are convinced of a causal effect. While this is possible, other interpretations are also consistent with the data. Even if there is a causal effect, the strength of the effect is rather small.”

Some associations appear with only a few prescriptions for a drug and do not show a marked increase with increasing numbers of prescriptions, and virtually all of the associations are diminished when adjustment is made for factors that differ between users and non-users of a drug that are not due to the drug itself, he explained.

“All patients should not be given unnecessary drugs, but this paper should not be used to stop drugs that are having benefits in individual patients for the conditions for which the drugs are prescribed.”

A spokesperson for the Medicines and Healthcare Regulatory products Agency said: “Patient safety is our highest priority and we continuously monitor the safety of all medicines on the UK market. These findings will be carefully evaluated, as with any study, to determine whether they have any implications for the safe use of anticholinergic medicines.”

*Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ 2018; 361: k1315.

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