Anticholinergic drugs and the risk of dementia: a nested case control study.
What is the aim of the study and why is it important?
Dementia is a common condition in older people, with serious consequences for affected individuals and their families and carers. Several factors can increase the risk of developing dementia such as older age, obesity, smoking, alcohol and having other illnesses such as diabetes, depression and stroke.
There is also some concern that certain medicines called anticholinergic drugs might increase the risk of developing dementia. Anticholinergic medicines are prescribed for treating a range of different medical conditions such as asthma, incontinence, dizziness, depression and insomnia. These medicines can cause side effects, such as confusion and memory loss especially in the elderly. Some recent research has indicated that anticholinergic medicines might also increase the risk of dementia, especially if they are taken for a long time. However the research studies which looked at this were mainly small, of short duration and they did not account for the effects of some of the other risk factors for dementia.
The study we are carrying out aims to find out whether use of anticholinergic drugs does seem to increase the risk of dementia.
How is the research being done?
The study has used information recorded in the QResearch database to carry out a case-control study. We have selected a group of people aged 55 and over who have been diagnosed with dementia (cases). We have also selected a similar group of patients who haven’t been diagnosed to dementia to use as a comparison group (controls).
We are looking at the information that both groups of people had recorded in their medical records to see how many people had prescriptions for anticholinergic drugs, and how long they had taken them for. We will use this information to see whether people with dementia were more likely to have been prescribed anticholinergic drugs in the past than the comparison group of people without dementia. We will account for other differences between the groups, such as age, obesity and other illnesses in the analyses of the data.
We will also look at some specific types of anticholinergic medication such as antidepressants to see whether there are different risks for any particular types of anticholinergic medication.
This research will help to establish whether anticholinergic medicines increase the risk of dementia, and will have implications for prescribing of these medicines.
Location of research
Nottingham and Oxford
Date on which research approved
Project reference ID
Generic ethics approval reference
Are all data accessed are in anonymised form?
Brief summary of the dataset to be released (including any sensitive data)
Men and women aged 55+ between 2004 and 2015 diagnosed with dementia or prescribed medication for dementia (cases) matched to 5 controls without dementia matched by age, sex, practice and calendar time.
GP data includes diagnoses and medication for dementia along with prescriptions for anticholinergic drugs, antidepressants, antipsychotics and risk factors for dementia.
Linked mortality data for diagnoses of dementia
What were the main findings?
There was an increased risk of dementia associated with use of anticholinergic drugs after accounting for other risk factors for dementia.
Results showed that there was a 49% increased risk of dementia for individuals in the highest category of anticholinergic drug use (>1095 total standardized daily doses; equivalent to taking one anticholinergic drug daily at the standard dose for 3 years) in the 1 to 11 years before diagnosis compared with those who had not taken anticholinergic drugs.
There were higher risks in people with dementia diagnosed before the age of 80 years and also in people diagnosed with vascular dementia rather than Alzheimer's disease.
The study results showed that there were increased risks of dementia specifically for the anticholinergic antidepressants, antipsychotic drugs, anti-Parkinsons drugs, bladder drugs and epilepsy drugs studied. Other types of anticholinergic drugs, such as antihistamines, and gastrointestinal medications, did not show increased risks of dementia.
What are the implications of the results?
The study strengthens a growing body of evidence showing that strong anticholinergic drugs have long term associations with dementia risk, and highlights which specific types of anticholinergic drugs have the strongest associations. This study cannot provide conclusive evidence that these drugs cause dementia, as the link could be due to other factors not assessed in the study. However, if the association is a casual effect the results indicate that around 10% of dementia diagnoses could be due to anticholinergic drug exposure.
The authors recommend that the potential risks of this type of medication should be carefully assessed by healthcare professionals alongside the benefits when the drugs are prescribed and that alternative treatments should be considered where possible. These findings also highlight the importance of carrying out regular medication reviews.
The authors wish to thank the practices who contribute to the QResearch database.
The project is funded by the National Institute for Health Research (NIHR) School for Primary Care Research.
Carol Coupland, Trevor Hill, Julia Hippisley-Cox, Tom Dening, Richard Morriss: University of Nottingham Michael Moore: University of Southampton
Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study
Authors: Coupland CA, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J
Ref: JAMA Intern Med doi 10.1001/jamainternmed2019.0677
Association of Anticholinergic Drug Exposure With Increased Occurrence of Dementia—Reply
Authors: Coupland CA, Moor M, Hippisley-Cox J
Ref: Association of Anticholinergic Drug Exposure With Increased Occurrence of Dementia—Authors Reply. JAMA Intern Med. 2019;179(12):1730-1731. doi:10.1001/jamainternmed.2019.4908
- JAMA Network Articles of the Year 2019 - QResearch Study Has Second Highest Read Rate of 2019 03/12/2019