Common Drugs May Cause Cognitive Problems

Neurology Now
July/August 2008
Volume 4(4)
pp 10,11
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Anticholinergic drugs are prescribed for a wide range of medical conditions, such as acid reflux, Parkinson's disease, high blood pressure, and urinary incontinence. These drugs work by blocking a chemical called acetylcholine that is required for memory. Now, some scientists worry that these drugs may seep into the brain and alter cognition.

This discovery started with a simple observation from Jack Tsao, M.D., a neurologist at the Uniformed Medical Services University in Bethesda, MD, and his colleague Kenneth Heilman, M.D., a neurologist at the University of Florida in Gainesville. Dr. Tsao was examining a 74-year-old woman who had suddenly started having hallucinations and memory problems. Before conducting extensive tests to see whether she had Alzheimer's, he looked for any possible new medicines that could be responsible for her acute symptoms. She had recently begun taking 2 milligrams of tolterodine (Detrol), a medication for overactive bladder. The symptoms seemed to coincide with the medication. Dr. Tsao asked her to stop taking it, and within weeks, her symptoms disappeared—specifically, the ability to lay down memories. Dr. Tsao presented the findings recently at the American Academy of Neurology annual meeting in April.

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Cholinesterase inhibitors like donepezil (Aricept) have been used to treat Alzheimer's disease for nearly two decades. These drugs have the opposite effect of anticholinergics—they inhibit the enzyme which breaks down acetylcholine, allowing more of it to be used by the brain. And while it's been known for some time that older people with dementia should not be given anticholinergic drugs because their symptoms worsen, no one knew what the effect would be in a population of normal people.

Dr. Tsao contacted David Bennett, M.D., and Raj Shah, Ph.D., of Rush University in Chicago, IL, who had been following cognitively healthy priests and nuns for more than 15 years as part of the Rush Religion Orders Study to identify possible risk factors for dementia; 870 had been followed up at least once over a seven-year period. Their information came with complete medical work-ups and a battery of neuropsychiatric tests. In addition, every medication they took throughout the study was logged.

The question was simple: Were people who began taking medicines with anticholinergic properties scoring worse on cognitive tests during the time they took these medicines?

The answer, they reported, was yes. They compared 191 people who had never taken medication with anticholinergic properties and 679 who had. The rate of cognitive decline after they started taking these medicines was more rapid. Their performance scores fell off 1.5 times more quickly than those who had not taken any of these types of medicines over the follow-up period. They did not find an increase in the number of people diagnosed with Alzheimer's.

“These drugs are not supposed to cross the blood-brain barrier,” said Dr. Tsao. “But clearly if they are interfering with memory they are probably entering the brain. We believe the effect may be widespread.” In fact, they did find more of a change in cognitive scores among those who were taking the medicines with the strongest anticholinergic effects, such as the ones that were used to treat overactive bladder.

“We could be moving into cognitive decline earlier than expected. It has tremendous implications,” Dr. Heilman says. Other studies need to be done to replicate their finding. In addition, the study was not large enough or long enough to test whether these medicines would increase a person's risk of developing Alzheimer's. However, Dr. Tsao says, “Physicians should be aware that some of these medicines interfere with cognitive functioning” even in mentally healthy patients.

—Jamie Talan

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