Drugs taken by millions for incontinence, depression and Parkinson’s may increase risk of dementia, finds study

Anticholinergics control involuntary muscle contractions but have a significant impact on memory function

Drugs used by millions of people to treat bladder problems or depression may increase their risk of developing dementia in later life by as much as a third, UK researchers have warned.

As many as two million people in England are being prescribed anticholinergic medications to control muscle contractions or help their mental health conditions, but which might actually cause mental declines later on.

Doctors have known for a while that these drugs can impair memory function and attention while they are being taken and can cause a sharp decline in the condition of older people.

However, new research led by scientists at the University of East Anglia (UEA) suggests that the taking them for over a year could increase the likelihood of people developing dementia up to 20 years later.

“We found that people who had been diagnosed with dementia were up to 30 per cent more likely to have been prescribed specific classes of anticholinergic medications,” said Dr George Savva from UEA’s School of Health Sciences and the lead author of the study published in the BMJ today.

“The association with dementia increases with greater exposure to these types of medication,” he added.

In a briefing, Dr Savva and his fellow authors authors said everyone's risks would be different, based on their treatment, genetics and lifestyle.

As a general rule, they explained that someone with a ten per cent risk of developing dementia in the next 15 years would see that increase to 13 per cent if they had been on anticholinergics for a year or more - or a "one in 33 chance of getting dementia you would otherwise not have got."

While the risks at an individual level are small, this should reinforce guidance to doctors about taking older people off these drugs and looking more closely at the combined effects of drugs as more people are put on multiple prescriptions.

In the largest study to date, the team reviewed prescribing and diagnosis data in GP records for 40,770 patients aged 65 to 99 who were diagnosed with dementia between 2006 and 2015, and nearly 300,000 without the condition.

The UEA team said that they thought there were one-and-a-half million to two million people in the UK taking anticholinergic drugs with a link to dementia.

The biggest effect was in drugs used for bladder disorders; such as oxybutynin and tolterodine; antidepressants, including amitriptyline and paroxetine; and Parkinson's disease, including benzatropine and procyclidine.

The study did not find an increased dementia risk from anticholinergics commonly used for stomach cramps, hay fever and travel sickness.

These types of medication all interfere with acetylcholine, a neurotransmitter chemical which is important in nerve cell signalling in the brain and around the body and has an important role in memory function.

Acetylcholine is the neurotransmitter that is also depleted in people with Alzheimer’s disease, the most common cause of dementia, which is set to affect one million people in the UK by 2025.

Around one-in-five patients with depression in the UK is on an anticholinergic.

Dr Ian Maidment from Aston University, the lead pharmacist on the study, said experimental data on the long-term impacts of these drugs was hard to obtain because clinical trials are so short.

"This study shows that some anticholinergics may cause long-term harm in addition to short-term harm, he added.

"With many different medicines having at least some anticholinergic activity, one focus should be de-prescribing. Doctors, nurses and pharmacists need to work with older people and their carers to ensure that they only take medication if the benefits clearly outweigh the harms."

Independent experts cautioned this could account for some of the increased risk, because depression is an early sign of the onset of dementia, and so anticholinergic treatment could be linked with dementia but not necessarily have caused it.

It was also important to note that more modern drugs recommended for treating urinary incontinence or depression are engineered to have much less effect on the brain, they said.

However, if the study is correct then around 20,000 more people in the UK would be likely to develop dementia because of current prescribing, the UEA team estimated.

“This is a large and very well conducted epidemiological study showing an 11 per cent increase in the incidence of dementia in people who have been treated with drugs that include, as a side-effect, strong action against the neurotransmitter acetylcholine in the preceding four to 20 years,” said Rob Howard, professor of old age psychiatry at University College London, who was not involved in the study.

“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.”

However, he said this study on its own could not prove the drugs alone had caused dementia, and stressed that anyone taking these medications should talk to their doctors before stopping or changing their prescription.