Neuroscientists have been warning for years that a class of medications called anticholinergic (AC or aCH) drugs are bad for your brain. That’s because AC drugs interfere with a crucial neurochemical called acetylcholine and alter brain cell function.
The studies keep accumulating. The latest was published in the highly regarded journal Neurology (online, Sept. 2, 2020). The authors point out that Alzheimer’s disease (AD) is increasing and that there are few, if any, “reliable treatments.”
The investigators note that reducing exposure to drugs that interfere with the actions of acetylcholine could be an important step in reducing the risk of AD. They also suggest that the “cognitive changes associated with aCH are often underappreciated.” In other words, doctors, nurse practitioners, PAs and pharmacists may not realize how many drugs have anticholinergic activity and how harmful they may be.
The Study on Anticholinergic Drugs and Brain Function:
The researchers recruited 688 older people who were deemed “cognitively normal” at the start of the study. They were followed for a decade. There was neuropsychological testing to asses things like language, attention, executive function and memory.
In addition, each participant was analyzed for exposure to anticholinergic drugs. The investigators were able to evaluate the anticholinergic “burden” each person was exposed to by determining how many aCH drugs were on board and how strong the anticholinergic activity might be.
Bad News for Brain Function:
One third of the people in the study were taking anticholinergic drugs. Of these 230 individuals, 73 had a high aCH burden. In a nutshell, here are the conclusions in the authors’ own words:
“Our results demonstrate that use of aCH [anticholinergic medication] in cognitively normal, highly educated, and healthy older adults is associated with increased risk of progression to MCI [mild cognitive impairment] and accelerated cognitive decline, which are exacerbated in the presence of AD [Alzheimer’s disease] biomarkers.”
Those participants with genetic risk factors for Alzheimer’s disease were two to four times more likely to start noticing memory and language problems.
What makes this study stand out was the long time frame. Over the 10-year study period the investigators were able to observe memory and language decline. They were also able to detect a greater risk of cognitive impairment associated with stronger anticholinergic drugs and a larger aCH burden. We found these words especially worrisome:
“Whether cumulative use of multiple ‘weaker’ aCH is tantamount to use of one ‘strong’ aCH remains unknown. However, it is clear from our results that use of aCH in general has detrimental consequences on cognitive functioning in older adults.”
Not the First Study:
We have lost count of the number of studies that demonstrate a link between anticholinergic medications and cognitive decline. Researchers have been reporting for years that anticholinergic medicines such as diphenhydramine could affect mental performance. Back in 2016, scientists wrote in JAMA Neurology (June 1, 2016):
“The use of AC medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of AC medication among older adults should likely be discouraged if alternative therapies are available.”
What the Research Uncovered about Anticholinergic Drugs:
The investigators studied 451 older people who were considered “cognitively normal” at the start of the research. The scientists tested people for their memory and mental functioning over the course of the trial. Some were given sophisticated PET scans to assess glucose uptake, a measure of neuronal activity. Others got scans utilizing MRI technology to determine the size and shape of their brains.
The goal of the research was to see whether medications with anticholinergic activity affected brain physiology and mental capability–things like memory, problem solving, planning ability and basic thinking.
The bottom line from this research appears to be that AC medications are bad for your brain! Not only did the drugs affect cognitive ability, they also reduced glucose metabolism in the hippocampus, an area of the brain critical for normal memory consolidation. There was also a relationship between the use of AC medicine and brain structure. The greater the anticholinergic “burden” the more brain deterioration was observed.
In Their Own Words:
Please do not take our word for this research. Here is what the investigators found:
“Use of medications with medium or high AC effects in the ADNI cohort was associated with poorer cognition (particularly in immediate memory recall and executive function), reduced glucose metabolism, whole-brain and temporal lobe atrophy, and clinical decline. The effect appeared additive because an increased burden of AC medications was associated with poorer executive function and increased brain atrophy. Similar effects were seen in an independent cohort of older adults. These results suggest that medications with AC properties may be detrimental to brain structure and function, as well as cognition.”
In other words, drugs with anticholinergic activity are bad for your brain. The more medicines you take with AC action, the worse the impact.
We’ve Been Warning About Anticholinergic Drugs for Years!
This recent research is new, but the general picture is not. Doctors have known that anticholinergic drugs could alter brain function for more than 100 years. At the beginning of the 20th century, German obstetricians began giving women in labor a powerful AC drug called scopolamine together with morphine.
They called this “twilight sleep.” They found that women would not remember the pain or anything else about the delivery process. These physicians described it as:
“clouded consciousness with complete forgetfulness.”
That should have been a tip off that AC drugs were scrambling neurons. Health professionals assumed it was a short-term effect and pretty much ignored the long-term consequences of administering AC medicine to millions of patients.
Do Doctors Know About Anticholinergic Drugs?
Physicians get surprisingly little training about AC drugs. They learn about medications such as atropine, hyoscyamine and scopolamine, which have been used to treat diarrhea and what was once called spastic colon and is now frequently referred to as IBS (irritable bowel syndrome).
Perhaps you have heard of Lomotil (a combination of atropine and diphenoxylate). It has been prescribed for decades to combat diarrhea. And scopolamine (Transderm Scop) has been a mainstay in the treatment of motion sickness.
What many health professionals do not realize, however, is that there are dozens of other drugs with AC activity. Over-the-counter antihistamines such as brompheniramine and diphenhydramine are considered anticholinergic medications. If you don’t recognize the name diphenhydramine, consider all the nighttime pain relievers. What turns Advil, Aleve, Bayer, Excedrin and Tylenol into “PM” drugs is diphenhydramine.
The motion sickness medicine Dramamine is also a potent AC drug containing the ingredient dimenhydrinate (which is in part diphenhydramine). Oh, by the way, the popular allergy medicine Benadryl is also diphenhydramine.
Ask your doctor about the antidepressant paroxetine (Paxil), the vertigo drug meclizine (Antivert) or the medicine for overactive bladder symptoms oxybutynin (Ditropan). These are all AC drugs.
The Anticholinergic “Burden”
The point is that there are dozens and dozens of drugs with AC activity. While taking one such med for a few weeks or months probably won’t be terribly bad for your brain, we do worry about what the researchers call the total anticholinergic burden.
Someone who is taking a nighttime PM pain reliever together with a medicine for overactive bladder plus a certain type of blood pressure pill might be getting a large dose of anticholinergic activity. That could be quite bad for the brain over the long haul. Many people may not realize that their brain fog or memory lapses could be due to the medications they are taking.
Protecting Your Precious Brain!
When you think about your health, where do you focus? Are you working to prevent heart disease, worried about cancer or concerned that your cognitive capacity might fail?
These topics are all worth your attention. However, while health care professionals usually do a good job prescribing drugs to reduce the risk of heart disease and screenings to detect certain cancers, they may not recognize all the medications that could contribute to brain failure. You may need to do that yourself.
Always ask the prescriber whether any of the medicines you take interferes with normal acetylcholine action. Medicines for overactive bladder are notorious for their anticholinergic activity. So are some antidepressants, especially amitriptyline and paroxetine. You should never stop such drugs on your own but do ask the doctor or nurse practitioner about switching to a different treatment.
As we stated, even over-the-counter drugs can have substantial anticholinergic activity. This reader wrote:
“Both my mother and mother-in-law were diagnosed with Alzheimer’s. Mom was 76, my mother-in-law 72. They lived very different lifestyles. Mom dealt with severe anxiety and depression, while my mother-in-law was a happy-go-lucky, very active and vivacious health nut.
“The only common denominator they share is they both took Benadryl to sleep on their doctors’ advice. Of course, our mothers could have had Alzheimer’s anyway. I do believe Benadryl exacerbated the tendency. We must be our own health care advocates and advocate for our elderly loved ones as well.”
Finding a List of Anticholinergic Drugs:
It can be difficult to find a comprehensive list of various types of anticholinergic drugs. That is why we compiled the most complete list we could find and put it on this website for you. If you would like to know whether your medications might have anticholinergic activity, you may want to consult this list we compiled for you. You may also wish to read stories from readers who have experienced mental side effects from anticholinergic drugs.
You may also want to read our book, Top Screwups Doctors Make and How to Avoid Them. In our chapter on older people we discuss the problem of anticholinergic drugs in far greater detail.
Never stop a medication suddenly and be sure to check with your doctor before discontinuing any prescription drug. Please vote on this article at the top of the page and leave your story in the comment section below. You may also want to share this article with friends and family. You can do so by scrolling to the top and clicking on the icons for email, Facebook or Twitter. Thank you for supporting our work.