High-Dose Anticholinergic Drugs May Increase Dementia Risk

Previous studies have suggested that medications—both prescription and over the counter—aiming to block the actions of acetylcholine may be associated with increased risk for cognitive impairment, but a recent study published in JAMA Internal Medicine shows that use of such medicines in older adults may increase the risk for dementia.

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Researchers from the Geriatric Pharmacy Program at the University of Washington led a large-scale study with older adults to examine whether a correlation exists between cumulative anticholinergic drug use and the onset of dementia.

“There are many medications with anticholinergic properties that impair cognitive performance,” said Davangere Devanand, M.D., director of the Division of Geriatric Psychiatry at the New York State Psychiatric Institute, who was not involved in the study. “Recognizing the cognitive impact of anticholinergic medications is very important for the well-being of patients,” he told Psychiatric News.

According to the study, medications with anticholinergic activity are widely used by older adults for an array of conditions, including overactive bladder, seasonal allergies, and depression. Previous studies have shown that the prevalence of anticholinergic use in older adults ranges from 8 percent to 37 percent.

To ascertain patients’ cumulative anticholinergic exposure, the researchers analyzed 10 years of pharmacy-dispensing data on 3,400 individuals aged 65 and older who had no history of dementia at the study’s initiation.

The results showed that individuals taking daily dosages of at least 10 mgs of tricyclic antidepressants, 4 mgs of first-generation antihistamines, or 5 mgs of antimuscarinics for bladder control for more than three years were at greater risk for developing dementia than their counterparts who did not use such medicines long term.

The researchers noted that the study highlights the need to increase awareness among health care professionals and older adults about the potential risk associated with extended use of anticholinergic drugs as well as a need for efforts to minimize such drug use.

“Older adults should be aware that many medications—including some available without a prescription, such as over-the-counter sleep aids—have strong anticholinergic effects,” said the study’s lead author, Shelly Gray, Pharm.D., M.S., director of the geriatric pharmacy program. “If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient,” Gray stated, “they should use the lowest effective dose, monitor the therapy regularly to ensure it’s working, and stop the therapy if it’s ineffective.”

“Physicians prescribing anticholinergics need to monitor the medicines’ impact on patients’ cognitive abilities and, consequently, functional abilities,” said Devanand. Measuring such abilities, he suggested, can be achieved by open-ended questioning of patients and caregivers and by serial administration of brief cognitive assessments such as the Mini-Mental State Examination and the Montreal Cognitive Assessment.

As for Gray and colleagues, she said that future studies with postmortem brain tissue are under way. The researchers plan to investigate differences, if any, of dementia-related pathology between brains that were exposed long term to anticholenergic drugs and those that were not.

The study was funded by the National Institute on Aging. ■