Do Anticholinergics Increase Dementia Risk?

A recent study has found that a class of drugs known as anticholinergics may increase the risk of dementia in patients aged 55 years and older. Commonly used in antidepressants, antihistamines, and antimuscarinics, the drugs have long been associated with side effects like confusion and memory issues. The new study, published in JAMA Internal Medicine, suggests more powerful side effects than medical professionals have previously understood.

As a report by the New York Times explains, anticholinergics encompass a variety of medications. Examples include clozapine, an antipsychotic; diphenhydramine, an antihistamine used in Benadryl, among other products; paroxetine, an antidepressant; tizanidine, a muscle relaxant; and scopolamine, an anti-nausea medication. Anticholinergics owe their wide range of applications to their function in blocking acetylcholine, a neurotransmitter involved in nervous system functions like muscle regulation, respiratory activity, digestion, and the opening and contraction of blood vessels. “Older adults are more likely to be prescribed many of these medications,” the Times explained, “simply because they tend to have more health issues.”

The JAMA Internal Medicine study examined 58,769 patients who had been diagnosed with dementia, with 225,574 matched control patients. Researchers examined dementia patients’ medical records, scrutinizing what medications doctor prescribed them between eleven years and one year before they were diagnosed with dementia. The study took into account 56 separate anticholinergic drugs, accounting for the dosage patients were prescribed and the length they were prescribed the drugs in question. What researchers ultimately discovered was a 50% increase in the risk of dementia in patients “who used a strong anticholinergic drug daily for about three years within that 10-year period,” according to the Times. This risk was strongest in patients who used anticholinergics to treat depression, psychosis, epilepsy, and bladder regulation issues. The study also found a stronger association between anticholinergics and dementia in patients who received their dementia diagnoses before they reached 80 years of age, and in patients with vascular dementia in comparison to those with Alzheimer’s disease.

The study’s authors caution that its results do not conclusively establish a causative relationship between anticholinergics and dementia, only that the risk of dementia appears to be increased among patients who take such medications. They also emphasize that the conditions patients take anticholinergics for may themselves be early warning signs of dementia: Depression, for instance, may be connected to an underlying condition that also leads to dementia. As such, the authors call for further research into the possible effects of weaning patients off anticholinergic medications.

What does all this mean for patients who are currently taking, or may be prescribed anticholinergic medications? Not much—yet. One expert told Time Magazine, “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.” Meanwhile, the Times recommended patients in need of long-term treatment for conditions that may require anticholinergics ask their doctors if other drug classes are available. “In many cases,” the report concludes, “there may be choices.”

To learn more about possible links between anticholinergic medications and the development of dementia, read the full JAMA International Medicine study here.

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