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New research suggests that some over-the-counter drugs increases the risk of neurodegeneration in adults over the age of 65.

Luke Sharrett/Bloomberg

Seniors, the next time you shop for hay-fever medicine, you may want to talk to a doctor or pharmacist.

A large U.S. study published last week in JAMA Internal Medicine found that adults over the age of 65 who frequently used certain medications – including common over-the-counter drugs – for a variety of conditions including allergies, insomnia, overactive bladder and depression, had an increased risk of developing dementia.

The researchers focused on anticholinergic medications, which are drugs that block acetylcholine, a neurotransmitter, from binding to receptors, called cholinergic receptors, that are located throughout the body. These included non-prescription medications, such as the allergy drug diphenhydramine, known by the brand name Benadryl.

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Researchers found a dose response relationship between anticholinergic medications and the risk of dementia, which means individuals who took larger doses of the drugs or for longer periods had a greater risk of developing dementia, including Alzheimer's disease.

"Our main message is first, we don't want older adults to panic," says lead researcher Dr. Shelly Gray, a professor in the department of pharmacy at the University of Washington in Seattle. But, she continued, "I think many older adults think that over-the-counter medications are safe. And we would just like people to be aware that even common medications used to help people sleep can have some of these anticholinergic medications in them."

Experts on neurodegenerative diseases have long known that anticholinergic medications can cause cognitive impairment, which was believed to be reversible once individuals stopped using them. But Gray says the latest findings suggest anticholinergics may be associated with lasting damage.

The study included more than 3,400 seniors and examined the medications they used over a 10-year period. About 20 per cent of the participants were found to use anticholinergics. Among the most common were older antihistamines, such as chlorpheniramine; antimuscarinics – such as oxybutynin – used for bladder control; and tricyclic antidepressants, such as doxepin.

The researchers found the greatest risk of dementia among individuals who took the equivalent of four milligrams a day of chlorpheniramine, five mg a day of oxybutynin and 10 mg a day of doxepin for more than three years. (If you're unsure whether an over-the-counter medication is anticholinergic, Gray suggests consulting a pharmacist.)

Although the study does not prove a causal relationship, Gray says it does provide more reason for seniors to avoid anticholinergics when possible and for their physicians to prescribe alternative medications when they can. She added that more research is needed to examine the biological mechanisms underlying the link. Moreover, it's unknown how anticholinergic medications may affect younger healthy individuals, including children, in the longterm.

"We don't understand totally how these medications might be causing permanent damage in the brain," she says.

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Dr. Sandra Black, a senior scientist at Toronto's Sunnybrook Research Institute who focuses on neurodegenerative diseases, says doctors who specialize in dementia typically try to take their patients off any anticholinergic medication unless they're essential, since these drugs interfere with the cholinergic system, which plays an important role in mental focus.

"This has been known for a long time," says Black, who was not involved in the JAMA study. But she says the study "really emphasizes this is something we have to be very vigilant about."

The study, however, does have limitations, says Dr. Carmela Tartaglia, a neurologist at the Krembil Neuroscience Centre's Memory Clinic at Toronto Western Hospital, who was not involved in the study. For instance, Tartaglia notes that participants who used anticholinergics also were more likely to be women, to rate themselves as having fair or poor health, have higher levels of depressive symptoms and take benzodiazepine medications than those who didn't use anticholinergics. Although the researchers corrected for such factors, Tartaglia says these "confounding factors … should be considered seriously" as it could be possible that some of these other factors were linked to the risk of developing dementia.

Tartaglia adds that there are some cases in which anticholinergic medications may offer patients necessary relief. It's difficult, for example, to find alternative medications for bladder control. If you have to get up multiple times a night to use the bathroom, you'll lose sleep and "you're going to be cognitively impaired," Tartaglia says. "You're really stuck in a hard place."

Nevertheless, she says, "If you can avoid using these medications, you should."

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