Anti-cholinergic Drugs – A Risk Factor For Dementia?

Recently, you may have read articles on the internet stating that certain medication prescribed for Parkinson’s disease (PD) and other conditions can cause dementia. Such an assertion is very worrying, but it is necessary to understand it in its context.

Let’s go to the source of this information. On April 25, 2018, researchers published an article in British Medical Journal entitled Anti-cholinergic drugs and the risk of dementia: case-control study. It is well known that anti-cholinergic medications can have negative effects on memory as a reversible side effect (meaning, the side effect will improve when the medication is stopped) and it is common for medications of this type to be weaned off as a patient ages or develops memory complaints.

This study however, took a closer look at whether these medications could cause cognitive problems that are not reversible when the medication is stopped, which is of particular interest to the PD population because anti-cholinergic medications can sometimes be prescribed to people with certain PD symptoms.

What are anti-cholinergic medications?

Anti-cholinergic medications block the action of acetylcholine, a chemical that allows certain nerves to communicate with each other. These nerves are found throughout the body and brain and affect a myriad of activities in the body. Different anti-cholinergic medications are designed to perform different tasks in the body and are therefore prescribed for a wide range of medical conditions including depression, urologic symptoms, asthma, pain, gastrointestinal complaints and cardiovascular disease. Anti-cholinergics can on occasion, be prescribed for motor symptoms of PD.

About the study

Researchers reviewed the Clinical Practice Research Database, which includes medical data on 11.3 million patients in the United Kingdom. From that database, 40,770 patients aged 65-99 with a diagnosis of dementia were selected and compared to 283,933 patients without dementia. Prescriptions of all the trial participants, from 4-20 years prior to time of data collection, were reviewed for exposure to anti-cholinergic medications.

What did the study find regarding anti-cholinergic medications and dementia?

The study found that there was an association between increasing total anti-cholinergic exposure and dementia diagnosis. Anti-cholinergic medications that are anti-depressants, urologic, and anti-parkinsonian were associated with increased dementia risk, but anti-cholinergics used for gastrointestinal or cardiovascular reasons, were not.

It’s important to note that overall, the increased risk of dementia was small.

Outlined in the paper is the following example: If a typical person aged 65-70 has a 10% risk of developing dementia over the next 15 years, exposure to a urologic medication with the highest degree of anti-cholinergic action would only increase that risk to about 12%.

The study claims an association between anti-cholinergic medications and dementia – that exposure to the drugs and a small increased risk of dementia tend to happen together. The study does not claim that exposure to drug causes this increased risk. This is an important difference. However, anything that might impact risk of dementia, needs to be carefully considered and discussed with your medical team.

Is it OK for me to take an anti-cholinergic drug if I have Parkinson’s?
PD patients may be taking anti-cholinergic medications for both motor and non-motor symptoms. Based on this study, you may be wondering if you should change your medication.
Some things to think about:

    • The study included two anti-cholinergic medications given for PD motor symptoms: amantadine and procyclidine. (FYI, Procyclidine is rarely prescribed in the US for PD, whereas amantadine is prescribed more widely.)
    • Trihexyphenidyl and benztropine which are sometimes prescribed for tremor in PD were not included in the analysis.
    • Because every medication has both risks and benefits, the need for amantadine, trihexyphenidyl or benztropine should be reviewed with the patient’s neurologist to determine if the positive benefits from the PD medication outweigh the potential small increase in dementia risk.
    • Other medications used for non-motor symptoms of PD were included in the study, namely anti-depressants and urologic medications. The anti-depressant class that is most anti-cholinergic in its effect is the Tricyclic anti-depressants (TCA). This class is not commonly used for patients with PD because of its side effects.
    • Paroxetine is a Selective serotonin reuptake inhibitor (SSRI) prescribed for depression. However, it also has anti-cholinergic properties and was therefore included in this analysis. Paroxetine is sometimes used for depression in patients with PD. If a patient with PD is on this medication and it is working well for depression, it may be worthwhile to stay on it, although it should be discussed with his/her neurologist or psychiatrist and other options can be considered.
    • Urologic medications that were considered in the study include tolterodine, oxybutynin and solifenacin. Patients with PD may be on these medications to control the urologic symptoms of PD. Again, these may be the best choice for a particular PD patient, weighing risks and benefits. Other options may be available however, so this should be discussed with the patient’s neurologist or urologist.

The bottom line is always twofold – the risks and benefits of medications must be weighed for each individual patient. In addition, patient medications should be frequently reviewed to monitor which meds are working and to incorporate any new available data.
Here are questions to ask your doctor about anti-cholinergic medications:

  1. Am I on any anti-cholinergic medications for PD motor or non-motor symptoms?
  2. Should we consider other options to control my symptoms?

Remember: your doctor may very well want you to stay on your current medications if her/she feels that the advantages outweigh the risk.

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