Despite the Headlines, We Don’t Yet Know If Anticholinergic Drugs Contribute to Dementia Risk

There are a number of things that can increase the risk of dementia: age, of course, as well as certain genetic profiles and behaviors such as smoking and drinking. Some of the same things that contribute to heart disease, such as high cholesterol levels and the build up of plaques in the blood vessels, can also boost the chances of developing dementia.

And in a large study published in JAMA Internal Medicine conducted in the UK, researchers report another possible factor: a group of drugs known as anticholinergics. These include prescription medications for treating depression, pulmonary disease, and Parkinson’s, as well as over-the-counter remedies for allergies. British researchers analyzed data from nearly 59,000 people with dementia as well as people without the condition and found that those who took the most anticholinergic drugs were 49% more likely to have developed dementia compared to those not taking the medications.

Anticholinergic drugs work by blocking a brain chemical called acetylcholine, which is critical for regulating muscles and for controlling messages sent to the nervous system. Previous studies have found side effects including memory loss and confusion linked to the drugs, so the British team wanted to investigate how these medicines might connect to dementia risk.

While the results are intriguing, they do not suggest that the medications are a definite risk factor for dementia. For one, the study was designed to detect only an association, and not a cause-and-effect relationship, between the drugs and dementia. Second, notes Yian Gu, an assistant professor in neurological sciences at Columbia University who was not involved in the study, the researchers could not fully discount the possibility that whatever condition prompted the patients to take the medications in the first place was actually connected to heightened dementia risk, and not the drugs themselves. For example, depression and sleep disturbances, two reasons anticholinergic drugs are prescribed, are often a precursor to Alzheimer’s dementia.

“This is a very large study and seems to be well designed,” says Keith Fargo, director of scientific programs and outreach at the Alzheimer’s Association, “but the issue for this kind of study is that no matter how well you design it, it’s impossible to control completely for all possible confounding variables.”

To truly see if anticholinergic drugs are contributing to dementia risk, researchers would have to take a group of people on the medications, ask them to stop taking them, and then compare their rates of dementia to those who continued to take them, to see if there were any differences.

That’s unlikely to happen, since the drugs are effective in addressing symptoms for many patients. For now, says Fargo, people who are on the medications should not stop taking them, and the findings, while interesting, aren’t likely to change the way doctors prescribe the drugs—at least until more research is done to clarify if, and how they might be influencing dementia risk. “I don’t think we’ll see people changing practice guidelines at this point, and people will likely still err on the side of treating conditions as effective as possible with these medications, rather than going all out to avoid them. It’s just too early to be doing that.”