Various commonly used drugs such as some over-the-counter sleep aids and hay fever pills, could be increasing the risk of developing dementia and Alzheimer’s in those over the age of 65. Although previous work has hinted that these drugs could have lasting effects on cognition, this is the first study to highlight a greater risk with higher use of the medicines; either from prolonged use or high doses.  

All of the drugs investigated in the new study, which involved more than 3,000 participants, have “anticholinergic effects,” meaning that they block a signaling molecule called acetylcholine in our nervous system.

Some drugs deliberately interfere with acetylcholine to achieve the intended therapeutic outcome, such as Ditropan (oxybutynin), which is used to treat an overactive bladder. Many pharmaceuticals, however, have unintended anticholinergic effects, including certain antihistamines such as Benadryl, or tricyclic antidepressants such as doxepin.

As noted in the study, it’s been known for some time that anticholinergic drugs can cause short-term impairment in certain aspects of cognition, such as memory and attention, even when just a single-dose is administered. However, it was generally believed that the effects on cognition are reversible if the drugs are stopped.

Recently, a couple of studies suggested that the drugs could also be linked with an increased risk of long-term cognitive problems, including dementia. But the studies were limited because they didn’t take into account the fact that some of the drugs may have been prescribed for early symptoms of undiagnosed dementia, such as depression, meaning the condition was already present when they began taking the medication.

Given the fact that up to 37% of older adults use these drugs, there exists a need to better understand the potential risks associated with their use, which is why the current study was set up. For the investigation, 3,434 individuals aged 65 or above were included, none of whom had dementia at the start. The researchers used pharmacy data to ascertain what anticholinergics they had been exposed to, and followed them up every 2 years for a decade.

Throughout the duration of the study, which has been published in JAMA Internal Medicine, 797 participants developed dementia, 89% of whom had Alzheimer’s. They found that the higher a person’s cumulative dose of anticholinergic medication, either through prolonged use or high doses, the greater the risk of developing dementia.

According to the results, individuals taking at least 10 mg/day of the tricyclic depressant doxepin (Sinequan), 4 mg/day of the antihistamine chlorpheniramine (Chlor-Trimeton), or 5 mg/day of oxybutynin for 3 years or more were at a greater risk of developing dementia.

Although the study can’t definitively prove that the drugs are causing the increased risk, the researchers said that pharmacists and doctors might want to consider prescribing alternatives that don’t exert anticholinergic effects when possible. Claritin, for example, could be used instead of Benadryl, or Prozac for depression. If alternatives can’t be used, then the lowest effective dose should be prescribed. They also caution that older people should not take this study to mean that they should stop taking their medication without speaking to their health care provider first.

[Via Group Health Research Institute, JAMA, BBC News and Live Science]