Cholinolytics and dementia
Widely used drugs with anticholinergic effect may increase the risk of dementia
Lina Medvedeva, XX2 century
A study conducted by experts from the University of Nottingham (University of Nottingham) showed that the risk of dementia among patients aged 55 years and older who took strong anticholinergic drugs for three or more years increases by almost 50%.
Anticholinergic drugs include: antipsychotic clozapine; a drug for bladder diseases darifenacin (sold as Emselex, an analogue of Enablex); scopolamine against nausea; bronchodilator ipratropium; muscle relaxant tizanidine (known as Sirdalud and Zanaflex); antihistamines such as diphenhydramine (brand name Benadryl, as well as Diphedrol), and antidepressants such as paroxetine (trademarks Adepress, Actaparoxetine, Paxil, etc.).
Anticholinergic (cholinolytic) drugs block acetylcholine, a natural neurotransmitter, replacing it with themselves when ingested due to the high affinity for cholinergic receptors of the brain.
Doctors prescribe such drugs for the treatment of various diseases, including chronic obstructive pulmonary disease, bladder diseases, allergies, gastrointestinal disorders and symptoms of Parkinson's disease.
These medications may have short-term side effects, including confusion and memory loss, but their less obvious effect is that they increase the risk of dementia.
The study, published in the journal JAMA Internal Medicine (Coupland et al., Anticholinergic Drug Exposure and the Risk of Dementia A Nested Case-Control Study), is based on the medical histories of 58,769 patients with diagnosed dementia and 225574 patients without such a diagnosis aged 55 years and older, registered in the QResearch database since January 1 2004 to January 31, 2016.
The results of the study showed an increased risk of dementia in those who took anticholinergic drugs in general and anticholinergic antidepressants, antipsychotic drugs, drugs against Parkinson's disease, bladder diseases and epilepsy in particular, taking into account other factors that increase the risk of dementia.
There was no increase in the risk of dementia associated with taking other studied anticholinergic drugs, such as antihistamines and drugs against gastrointestinal diseases.
Professor Tom Dening, head of the Dementia Centre at the University of Nottingham and a member of the research team, says: "This study provides additional evidence that doctors should be careful when prescribing certain drugs with anticholinergic properties. However, it is important that patients taking such medications do not stop taking them suddenly, as this can be much more harmful. If patients are worried about this, they should discuss it with their doctor to consider all the pros and cons of such treatment."
The average age of 58,796 patients with dementia was 82 years, 63% of them were women. Each case was compared with five control cases in patients of the same age, gender and general health condition.
The effect of anticholinergic drugs was evaluated using data on prescriptions over a 10-year period, 1-10 years before the diagnosis of Dementia, and also compared with the same period in patients from the control group. Further analysis took into account prescriptions for anticholinergic drugs prescribed 20 years before the diagnosis of dementia.
This is a non-experimental study, so it is impossible to draw unambiguous conclusions about whether anticholinergic drugs affect the development of dementia, and it may happen that they were prescribed for early symptoms of dementia.
Professor Copeland says: "Our study provides additional evidence of an increase in the potential risks associated with strong anticholinergic drugs, in particular antidepressants, anti-muscarinic drugs for the bladder, drugs against Parkinson's disease and epilepsy. Healthcare professionals should consider the risks associated with this type of medication, as well as the benefits associated with prescribing medications, and, if possible, consider alternative treatments, such as other types of antidepressants and other treatments for bladder diseases. These findings emphasize the importance of regular drug certifications. We found an increased risk in people diagnosed with Dementia at the age of 80, which indicates that anticholinergic drugs should be prescribed with caution to both middle-aged and elderly people."
These results, as well as the results of a similar study published in 2018, helped to identify which types of anticholinergic drugs are associated with the greatest risk of dementia.
From one year to 11 years before the date of diagnosis of dementia or its equivalent in the control group, almost 57% of cases and 51% of the control group were prescribed at least one strong anticholinergic drug. Most often, these were antidepressants, anti-dizziness drugs and antimuscarinic agents for the bladder.
The increased risk associated with these drugs indicates that if the link between them is the cause of about 10% of dementia diagnoses, this is a significant proportion of new cases of the disease per year. This is comparable to other factors subject to change, including 5% of new cases of hypertension in middle age, 3% in diabetes, 14% in smoking in old age and 6.5% in the absence of physical activity.
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