Summary: Anticholinergic drugs, commonly prescribed to treat a range of disorders, from Parkinson’s disease to bladder conditions, may increase dementia risks. The increased risk was linked to anticholinergic antidepressants, antipsychotics, bladder control, epilepsy and Parkinson’s disease medications. There were no increased risks associated with other types of anticholinergics, such as gastrointestinal drugs or antihistamines.
Source: University of Nottingham
The study, carried out by experts from the University of Nottingham and funded by the NIHR School for Primary Care Research, found that there was nearly a 50% increased risk of dementia among patients aged 55 and over who had used strong anticholinergic medication daily for three years or more.
Anticholinergic drugs help to contract and relax muscles. They work by blocking acetylcholine, a chemical that transmits messages in the nervous system.
Doctors prescribe the drugs to treat a variety of conditions, including chronic obstructive pulmonary disease, bladder conditions, allergies, gastrointestinal disorders and symptoms of Parkinson’s disease.
These medicines can have short-term side effects, including confusion and memory loss, but it is less certain whether long-term use increases the risk of dementia.
The research, published in the JAMA Internal Medicine journal and led by Professor Carol Coupland from the University’s Division of Primary Care, looked at the medical records of 58,769 patients with a diagnosis of dementia and 225,574 patients without a diagnosis of dementia, all aged 55 and over and registered with UK GPs contributing data to the QResearch database, between 1 January 2004 and 31 January 2016.
The study findings showed increased risks of dementia for anticholinergic drugs overall and specifically for the anticholinergic antidepressants, antipsychotic drugs, antiparkinsons drugs, bladder drugs and epilepsy drugs after accounting for other risk factors for dementia.
No increased risks were found for the other types of anticholinergic drug studied such as antihistamines and gastrointestinal drugs.
Professor Tom Dening, Head of the Centre for Dementia at the University of Nottingham and a member of the research study team, said: “This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties. However, it’s important that patients taking medications of this kind don’t just stop them abruptly as this may be much more harmful. If patients have concerns, then they should discuss them with their doctor to consider the pros and cons of the treatment they are receiving.”
The 58,769 patients with dementia had an average age of 82 and 63% were women. Each dementia case was matched to five control patients of the same age, sex, and general practice.
Anticholinergic drug exposure was assessed using prescription information over a complete period of 10 years from 1 to 11 years before diagnosis of dementia or the equivalent dates in control patients and was compared between the two patient groups. Further analysis looked at prescriptions for anticholinergic drugs up to 20 years before diagnosis of dementia.
This is an observational study so no firm conclusions can be drawn about whether these anticholinergic drugs cause dementia, and it is possible that the drugs were being prescribed for very early symptoms of dementia.
Professor Coupland said: “Our study adds further evidence of the potential risks associated with strong anticholinergic drugs, particularly antidepressants, bladder antimuscarinic drugs, anti-Parkinson drugs and epilepsy drugs.
“The risks of this type of medication should be carefully considered by healthcare professionals alongside the benefits when the drugs are prescribed and alternative treatments should be considered where possible, such as other types of antidepressants or alternative types of treatment for bladder conditions. These findings also highlight the importance of carrying out regular medication reviews.
“We found a greater risk for people diagnosed with dementia before the age of 80 which indicates that anticholinergic drugs should be prescribed with caution in middle-aged people as well as in older people.”
These results, along with those of a similar study published in 2018 help to clarify which types of anticholinergic drug are associated with the highest risks of dementia.
In the 1-11 years before the dementia diagnosis date or equivalent in controls, nearly 57% of cases and 51% of controls were prescribed at least one strong anticholinergic drug, with an average of six prescriptions in cases and 4 in controls. The most frequently-prescribed types of drugs were antidepressants, anti-vertigo and bladder antimuscarinic drugs—which are used to treat an overactive bladder.
The increased risk associated with these drugs indicates that if the association is causal around 10% of dementia diagnoses could be attributable to anticholinergic drug exposure, which would equate to around 20,000 of the 209,600 new cases of dementia per year in the UK.
This is a sizeable proportion and is comparable with other modifiable risk factors for dementia, including 5% for midlife hypertension, 3% for diabetes, 14% for later life smoking and 6.5% for physical inactivity.
Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study Importance Anticholinergic medicines have short-term cognitive adverse effects, but it is uncertain whether long-term use of these drugs is associated with an increased risk of dementia.
Objective To assess associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.
Design, Setting, and Participants This nested case-control study took place in general practices in England that contributed to the QResearch primary care database. The study evaluated whether exposure to anticholinergic drugs was associated with dementia risk in 58 769 patients with a diagnosis of dementia and 225 574 controls 55 years or older matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.
Exposures The primary exposure was the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia or equivalent date in matched controls (index date).
Main Outcomes and Measures Odds ratios (ORs) for dementia associated with cumulative exposure to anticholinergic drugs, adjusted for confounding variables.
Results Of the entire study population (284 343 case patients and matched controls), 179 365 (63.1%) were women, and the mean (SD) age of the entire population was 82.2 (6.8) years. The adjusted OR for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date. There were significant increases in dementia risk for the anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34), antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00), antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90), bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75), and antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57) all for more than 1095 TSDDs. Results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1095 TSDDs. Associations were stronger in cases diagnosed before the age of 80 years. The population-attributable fraction associated with total anticholinergic drug exposure during the 1 to 11 years before diagnosis was 10.3%.
Conclusions and Relevance Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.