Fall 2011

Drugs Linked to Cognitive Impairment and Increased Risk
of Death

By Karen Appold
Aging Well
Vol. 4 No. 4 P. 6

A study has linked certain medications, such as over-the-counter and prescription sleep aids as well as medications for allergies, depression, pain, nausea, hypertension, congestive heart failure, and incontinence, with having anticholinergic effects that can cause cognitive impairment and possibly early death in older adults.

Anticholinergics affect the brain by blocking acetylcholine (ACh), a nervous system neurotransmitter. ACh plays a major role in creating memory and the speed of reaction and communication in the brain. Therefore, taking drugs with anticholinergic effects can cause cognitive impairment such as difficulty remembering recent events, executing complicated tasks, or communicating.

A two-year study on the impact of these medications involving 13,000 men and women aged 65 and older was part of the Medical Research Council’s Cognitive Function and Ageing Studies, a large U.K.-based longitudinal multicenter study initiative looking at health and cognitive function in older adults. Results of the study appeared in the June 24 advanced online publication of the Journal of the American Geriatrics Society.

Over-the-counter products containing diphenhydramine, sold under various brand names such as Benadryl, Dramamine, Excedrin PM, Nytol, Sominex, Tylenol PM, and Unisom, have been shown to have anticholinergic activity. Other anticholinergic drugs, such as Paxil, Detrol, Demerol, and Elavil, are available by prescription.

Malaz Boustani, MD, an associate professor of medicine at the Indiana University Center for Aging Research, a scientist at the Regenstrief Institute, the study’s coauthor, and a geriatrician who directs the Wishard Healthy Aging Brain Center in Indianapolis, says it looks as though at least some of the effects of anticholinergics are reversible if the medication is stopped, although further research is needed to confirm this. “Some other studies have found an irreversible relationship between exposure to these medications and Alzheimer’s disease,” Boustani says.

Because the list of anticholinergic medications is lengthy, Boustani and colleagues developed the Anticholinergic Cognitive Burden Scale to evaluate the link between anticholinergic activity and cognitive decline. Available online and free of charge, the scale allows physicians to scan the medications documented in a patient’s electronic medical record (EMR), identify any anticholinergic medications, and suggest alternative medications.

“This is the best and most practical way to reduce exposure to anticholinergic medications and offer decision support to clinicians in the field,” Boustani says.

Calculating Anticholinergic Effects
The Anticholinergic Cognitive Burden Scale lists approximately 45 medicines that have anticholinergic activity. It rates each type of medication as having no anticholinergic effect (0), a weak anticholinergic effect (1), a moderate anticholinergic effect (2), or a strong anticholinergic effect (3). Then it calculates the effect of all of the patient’s anticholinergic medications. The physician then receives a total score, which in Boustani’s study ranged from 0 to 8. If a patient receives a score of 3 or higher, then Boustani would strongly recommend that the treating clinician advise using an alternative medication.

Clinicians who don’t have access to an EMR system or don’t control their own EMR system’s content can download a paper version of the scale. It contains a list of anticholinergic medications and rates them as having strong or weak anticholinergic activity. Alternatives to these medications are offered on the same page.
Boustani and colleagues at Wishard Health Services are currently working to develop software for the scale for an Apple iPhone application.

Weighing the Pros and Cons
Unfortunately, “The cognitive effects of anticholinergic medications are not well recognized in the field,” Boustani says. In addition, it is difficult to determine whether cognitive impairment results from a medication’s anticholinergic effects or something else.

“If a patient complains of cognitive impairment, a clinician’s first step should be to look at the patient’s list of both prescribed and over-the-counter medications and scan the list to see if there are any anticholinergic medications,” Boustani adds.

If so, the clinician should discuss the benefits vs. the risks of taking such medications or reducing the dosage. The physician may stop the medicine for three to six months and then perform a cognitive assessment to determine whether the patient notices a change. “Let the patient decide whether he or she favors the therapeutic benefit of their medications over the adverse cognitive effects,” Boustani says.

In particular, one such harm of anticholinergic medications could be an increased risk of mortality although more studies need to be done to prove this. The study by Boustani and colleagues evaluated individuals aged 65 and older and found that of those who took anticholinergics, 20% died within two years compared with 7% of those who didn’t take anticholinergics. “We don’t have detailed information regarding the period of exposure and how it relates to death. My group is currently investigating this with new studies,” Boustani says.

When they see him for treatment, many of Boustani’s patients are taking anticholinergic medications for urinary incontinence. After explaining the potential side effects on the brain, such as increasing by 50% the chance of developing cognitive impairment or doubling the risk of death over two years, almost nine of 10 patients choose to stop taking their anticholinergic medications. They prefer to use other strategies to help them with bladder issues, such as pelvic exercises, adult diapers, or scheduled toileting.

“As clinicians, we are well trained to pay attention to the side effects of medications on the kidney, liver, and cardiovascular system,” Boustani notes. “The brain is the only organ you can’t transplant and arguably it’s the most valuable, but for some reason we don’t pay enough attention to maintaining the brain’s health. Let’s strive to maintain the health of the brain, and hopefully we will have a better outcome.”

— Karen Appold is a freelance medical writer in Royersford, Pa.