Featured Review: The impact of medications with anticholinergic effects on future problems with memory and thinking

In this recently published Cochrane review, the author team explored whether taking a certain type of medication could make older people more likely to develop dementia. 

Discussing the review, Terry Quinn, senior author, said: "Almost every week we see a newspaper headline describing something new that allegedly causes or protects against dementia. These features attract attention as we all want to protect our brain health, but there is often little science behind the headlines.

There has been a lot of recent interest around whether certain prescribed medications can cause dementia. A class of medication frequently implicated in causing dementia are the ‘anticholinergics’. Medications with anticholinergic effects are commonly prescribed for conditions like hayfever, asthma, and urinary problems.

In this review we collated all the published evidence around anticholinergic prescribing and future risk of dementia. We found that taking anticholinergic medication long-term is associated with an increased risk of future dementia, and the more anticholinergic medications taken, the bigger the risk.

Reviews that look at whether a factor can predict future health require a different approach to the standard systematic review. These prognosis reviews are a relatively new method for Cochrane but are incredibly important for the dementia field.   

So, should people taking anticholinergic medications be worried? At the individual level, the risk of dementia was small and many of the included studies had issues that weakened the credibility of the results. However, older adults taking anticholinergic medications may wish to discuss with their healthcare provider whether their anticholinergic medications are still needed."

What was the aim of this review?

Medicines can be classified by their ability to block the action of a chemical signalling system in the body called the cholinergic system. Medicines that do this are said to have anticholinergic effects. There are various measurement scales to quantify the effects of anticholinergic medicines. The overall anticholinergic effect caused by all the anticholinergic medications a person is taking is referred to as 'anticholinergic burden.'

We aimed to investigate if older people who have no problems with memory or thinking are more likely to develop dementia when prescribed anticholinergic medicines than people who are not prescribed these medicines.

Anticholinergic burden ratings can vary with the scale used because different scales score medicines in different ways. Therefore, we also wanted to know if any particular anticholinergic burden measurement scale was more strongly associated with increased risk of dementia than other scales.

Key messages

There may be a link between anticholinergic medicine use and future risk of dementia. However, there are limitations in the published evidence, and we cannot say definitively if dementia is caused by the anticholinergic medicines themselves or by other factors. There were too few studies to allow us to compare the various anticholinergic measurement tools.

What was studied in the review?

There are more than 40 million older people worldwide living with dementia. These numbers are expected to rise to over 100 million by 2050 and at present there are very limited treatment options available. Therefore, it is important to identify factors that may increase the risk of dementia.

Because the cholinergic system in the brain plays an important role in learning and memory, there are theoretical reasons to believe that medications with anticholinergic effects could cause future dementia. Research has suggested that these medications may have unintended effects on memory and thinking, potentially resulting in dementia. If this is the case, one way to reduce the numbers of older people who develop dementia may be to avoid prescribing these medicines. Many commonly used medications have anticholinergic effects, for example medications for hay fever, insomnia (difficulty getting to sleep or staying asleep for long enough to feel refreshed), and depression.

In this review, the author team investigated the link between anticholinergic medicines, as measured by various measurement scales, and future dementia.

What were the main results of the review?

Review authors found 25 studies, including 968,428 people aged 50 years or more. Despite the relatively large number of studies, differences in design and methods only allowed authors to combine a few of them in analyses. They found that there is a consistent link between use of anticholinergic medicines and risk of future dementia. They cannot say if these medicines play a causal role; however, if they do, taking these medicines could potentially double a person's risk of dementia.

Of the anticholinergic measurement scales available, the author team could assess one commonly used tool – the 'Anticholinergic Cognitive Burden scale.' If this scale identified someone as having high anticholinergic burden, the risk of future dementia was more than two times higher than for someone with no anticholinergic burden.

The evidence included in this review was of a low quality overall and may have exaggerated the strength of the association between anticholinergic medicines and dementia. For example, anticholinergic medicines may be prescribed for the early symptoms of dementia. This would give a strong link but would not imply that the medicine caused the memory problems. Similarly, there is a risk that studies are only published when they show an association between anticholinergic medicines and future dementia. It may be that the only way to truly establish if anticholinergic medications are associated with future dementia would be to conduct a study where some people have their anticholinergic medications stopped or changed to an alternative and others continue their usual medications.

How up to date was this review?

The authors searched for studies published up to 24 March 2021.