Widely Used Drugs Tied to Greater Dementia Risk for Seniors

People over age 65 who frequently take over-the-counter sleep aids and certain other commonly used drugs may be increasing their risk of dementia, new findings show.

In the study, the researchers looked at drugs that have "anticholinergic effects," meaning they block a neurotransmittercalled acetylcholine. Many drugs fall into this class, including tricyclic antidepressants such as doxepin, antihistamines like Chlor-Trimeton (chlorpheniramine) and drugs like Detrol (oxybutinin) used to treat overactive bladder.

"We have known for some time that even single doses of these medications can cause impairment in cognition, slower reaction time, [and] reduced attention and ability to concentrate," said Shelly Gray, the study's first author and a pharmacy professor at the University of Washington in Seattle. Originally, "the thinking was that these cognitive effects were reversible when you stopped taking the medication."

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But Gray's study found a link between heavier use of these medications and dementia, "which is a nonreversible, severe form of cognitive impairment," she said.

Studies have shown as much as 37 percent of people over age 65 use anticholinergic medications, Gray and her team noted in their report, published today (Jan. 26) in the journal JAMA Internal Medicine. Some previous studies had linked the drugs to permanent cognitive changes, including dementia, but all of these studies had "important limitations," the authors wrote. [6 Foods That Are Good for Your Brain]

For example, some studies failed to take into account that some anticholinergic drugs are used to treat depression and insomnia, which can be early warning signs of dementia. "If you don't account for that, it looks like the medication is causing the dementia, while it's really those symptoms that are causing that anticholinergic use," Gray said.

In the new study, Gray and her colleagues looked at data from the prospective Adult Changes in Thought study, which includes patients from Group Health, a health-care delivery system in Seattle. The researchers identified 3,434 people who were ages 65 and older and were free from dementia at the start of the study.

During follow-up, which lasted an average of about seven years, 797 study participants (23.2 percent) were diagnosed with dementia, and about 80 percent of these individuals had Alzheimer's disease. The researchers found that the higher a patient's cumulative dose of anticholinergic medication over the 10 years before entering the study, the greater his or her risk of dementia.

A secondary analysis by the researchers showed that it didn't seem to matter when the patient had used the medications during the previous 10 years; it just mattered how much the individual had used in total.

The researchers also analyzed the data after omitting the patients' prescription information for the first year, or two years, before they were diagnosed with dementia. This was done to address concerns that the drugs might be used to treat what were actually the early signs of dementia. The results remained the same after the omissions, however.

Based on the findings, people who took 10 milligrams of doxepin daily for a total of three years would be at increased risk of dementia, the researchers said. The same was true of people who take  4 milligrams of chlorpheniramine daily, or 5 milligrams of oxybutinin daily.

"Some anticholinergic medications are important for older adults, so I would urge them not to stop taking any medications that are anticholinergic until they speak to their health care provider," Gray told Live Science, referring to prescribed medications. She also suggested that older people give their doctor a list of all the over-the-counter medications they use, "so that the health care provider can look for opportunities to reduce unnecessary anticholinergic medication use."

Some study participants have consented to postmortem brain autopsies, Gray noted. "We will be looking at whether those with high anticholinergic use also have brain pathology consistent with dementia to try and understand the underlying mechanisms," she said.

Noll Campbell and Malaz Boustani, of the Regenstrief Institute in Indianapolis and the Indiana University Center for Aging Research wrote a commentary accompanying the new study, where they argued that the adverse effects of these medications may be reversible, especially in the early stages.

In a statement, Campbell said the study's findings may be a result of the researchers using dementia as an outcome, instead of the less severe condition called mild cognitive impairment, which may be reversible in some older adults. "Our previous studies have shown a stronger association of these harmful medications with the diagnosis of mild cognitive impairment than with dementia," he said.

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