Commonly used drugs for problems like colds, allergies, depression, high blood pressure and heart disease have long been linked to cognitive impairment and dementia. Now researchers have some fresh evidence that may help explain the connection.
The drugs, known as anticholinergics, stop a chemical called acetylcholine from working properly in the nervous system. By doing so, they can relieve unpleasant gastrointestinal, respiratory or urinary symptoms, for example.
The list of such drugs is long. Among them: Benadryl for allergies, the antidepressant Paxil and the antipsychotic Zyprexa, Dimetapp for colds and the sleep aid Unisom.
In the new analysis, researchers looked at brain scans and cognitive test results from 451 older adults – including 60 who had been taking anticholinergic drugs for at least a month. The study participants were about 73 years old on average.
None of them had been diagnosed with cognitive problems like Alzheimer’s disease or dementia. But brain scans of people who used anticholinergic drugs showed lower levels of glucose processing in the brain – an indicator of brain activity – in a region of the brain associated with memory that’s also affected early in the course of Alzheimer’s disease.
In addition, patients who used these medications had reduced brain volume and thickness in some regions linked to cognitive function, the researchers report in JAMA Neurology. People who used these drugs also scored lower on tests of immediate memory recall and executive function compared to people who weren’t using these drugs, researchers found.
“There are definitely medical benefits to all of the anticholinergic medications we looked at, which could outweigh the cognitive risks,” said lead study author Shannon Risacher of the Indiana Alzheimer Disease Center at the Indiana University School of Medicine in Indianapolis.
“But if alternative therapies are available that provide effective treatment of these conditions, patients and doctors might want to consider avoiding anticholinergic medications,” Risacher added by email. The study can't prove the anticholinergics were the cause of participants' brain and memory differences.
The authors also acknowledge limitations of their study. In addition to the small number of participants taking anticholinergic drugs, another problem is that the study relied on participants to accurately recall and report on drug use, which wasn’t verified by medical records or prescription data.
This study and others like it are limited as well by a lack of specifics about what dosage of anticholinergic drugs people took or how long they used the medications, noted Alain Koyama, an outcomes researcher at Health Advocate, a consultancy in Los Angeles.
“Therefore, it is yet unclear if lower doses or shorter durations of use can in fact mitigate risk of cognitive harm,” Koyama, who wasn’t involved in the study, said by email. Still, the study adds to a growing body of evidence connecting anticholinergic medicines to cognitive problems later in life and offers new evidence to explain why this link exists, Koyama added.
The findings should encourage doctors and patients to discuss the drugs, and to consider whether the potential risk of cognitive decline merits avoiding or limiting use of these medicines. Not every patient will arrive at the same answer, however.
“Since the pathology underlying any effect of anticholinergic drugs on cognitive function likely takes years to manifest, if a patient is clearly benefiting from a drug in the short-term, but may not survive in the long term, any cognitive harm from the drug may be inconsequential,” Koyama said.
“On the other hand, a healthier patient particularly concerned about future dementia risk, whether because of family history or other reason, may consider alternative treatments,” Koyama added.
