The People's Perspective on Medicine

Anticholinergic Drugs and Dementia: The Link Gets Much Stronger!

Alzheimer disease is devastating. People assume it is caused by bad genes or bad luck. There are increasing data linking anticholinergic drugs and dementia.
Senior Adult.

We have been writing about the dangers of anticholinergic drugs and dementia for more than a decade. There are dozens of studies and hundreds of articles referencing anticholinergic drugs and dementia in the National Library of Medicine database.  Despite the preponderance of data supporting this connection, many health professionals are either unaware of this relationship or remain unconvinced that it is a real problem. As a result, many people are taking a number of anticholinergic drugs simultaneously. A new study in JAMA Internal Medicine (June 25, 2019)  suggests that may hasten cognitive decline. What is the big picture on anticholinergic drugs and dementia?

What is Acetylcholine and Why Is It Important?

Let’s nail down the basics. Acetylcholine (ACh) is a critical neurotransmitter. It can be pronounced a couple of different ways (ASS-se-TEAL-coal-EEN; AS-i-TILE-Koh-LEEN; uh-settle-COAL-lean). This crucial compound is responsible for a great many vital functions. Without ACh we would die in short order. It activates muscles. You could not walk, breathe or pick up a pencil without acetylcholine on board.

Acetylcholine and the Brain:

ACh is also essential to the central nervous system. It plays a critical function for learning and memory. When our cholinergic neurons (that make acetylcholine) become dysfunctional, we end up with memory problems and/or Alzheimer’s disease. The few barely effective drugs that are prescribed for Alzheimer’s are designed to boost the cholinergic nervous system.

Doctors should have realized that acetylcholine was crucial for brain function over 100 years ago. That’s because German obstetricians were intentionally trying to help women forget the pain of childbirth. They administered a cocktail of morphine and the drug scopolamine during labor and delivery. Women had no memory of what happened.

The doctors in Germany called this amnesia experience Dammerschlaf. It meant “twilight sleep.” They described the process as “clouded consciousness with complete forgetfulness.” You might think this would have been a red flag for neuroscientists. Instead, they assumed it was a short lived effect. That may have been true. But there is growing evidence that interfering with ACh over many years with drugs like scopolamine could well lead to cognitive dysfunction.

What Are Anticholinergic Drugs?

Scopolamine is a classic anticholinergic (AC) drug. It interferes with the ability of acetylcholine to reach and activate ACh receptors. Scopolamine is prescribed to prevent the nausea and vomiting of motion sickness (Transderm Scop). Scopolamine diminishes bodily secretions and intestinal contractions. The drug is sometimes given prior to surgery to reduce salivation.

Most health professionals know that scopolamine, and its chemical cousin atropine, are powerful anticholinergic drugs. The drug Lomotil (diphenoxylate plus atropine) is prescribed for people with diarrhea or a diagnosis of IBS (irritable bowel syndrome with diarrhea).

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Stealth Anticholinergic Drugs and Dementia:

What many health professionals do not realize is that there are scores of drugs on the market with anticholinergic activity. Researchers have begun speaking about the “anticholinergic burden” patients bear when they take more than one medicine with AC activity (BMC Geriatrics, March 25, 2015). 

“The cumulative effect of taking multiple medicines with anticholinergic properties termed as anticholinergic burden can adversely impact cognition, physical function and increase the risk of mortality.”

The Latest Research on Anticholinergic Drugs and Dementia:

British researchers reviewed the medical records of more than 250,000 people in primary care practices in the UK (JAMA Internal Medicine, June 25, 2019). 
There were nearly 59,000 individuals who had been diagnosed with dementia. Each one was matched to five controls of similar age who had no dementia diagnosis.

In looking back over more than a decade of prescriptions, the investigators found that people who had taken anticholinergic medicines were almost 50 percent more likely to get a dementia diagnosis. Those with greater total exposure had a higher risk. Pharmacologists call this a dose response curve. It is often considered convincing evidence that the effect is real. This also corresponds to other research on this general topic.

The authors conclude:

“Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people.

“The present study adds further evidence of potential risks associated with strong anticholinergic drugs, particularly those that are antidepressants, bladder antimuscarinic drugs, antiparkinson drugs, and epilepsy drugs.”

An accompanying editorial notes (JAMA Internal Medicine, June 25, 2019):

“The authors report an association between long-term use of strong anticholinergic medications and the diagnosis of ADRD [Alzheimer disease and related dementias], replicating findings from similar studies from various international populations.”

These scientists call for “deprescribing trials” that would test whether taking people off anticholinergic drugs would lower their likelihood of developing dementia.

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Other Research Linking Anticholinergic Drugs and Dementia:

As we mentioned, this is not the first study to suggest that anticholinergic drugs are associated with Alzheimer’s disease and/or other dementias. Eleven years ago we wrote about Catholic priests and nuns who had cognitive declines associated with anticholinergic drug exposure. You may find this early research of interest.

Some Drugs Dull Mental Edge

More than three years ago we posed this question:

Are Anticholinergic Drugs Bad for Your Brain?

How Would You Know if You Were Taking Anticholinergic Drugs?

Many health professionals are surprised to learn how many medications they prescribe have anticholinergic activity. Antidepressants like amitriptyline (Elavil) and paroxetine (Paxil) have significant anticholinergic activity. So do medicines for overactive bladder or incontinence such as oxybutynin (Ditropan) and tolterodine (Detrol).

You can learn more about the various drugs with AC activity at this link:

Commonly Prescribed Anticholinergic Drugs Linked to Dementia

Never stop any medicine without checking first with the prescriber. Some drugs with anticholinergic activity cannot be stopped suddenly. Others may be absolutely crucial for a serious health condition like Parkinson’s disease or congestive heart failure. If you are concerned about your anticholinergic “burden,” ask whether a difference medicine could be substituted.

If you would like to see a comprehensive list we have drawn up about anticholinergic drugs and dementia, here is a link:

Where Can I Find A List of Anticholinergic Drugs?

Protect yourself from adverse drug reactions of all sorts by reading our book, Top Screwups Doctors Make and How to Avoid Them.

Share your own experience with anticholinergic drugs in the comment section.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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Citations
  • Coupland, C. A., et al, "Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study," JAMA Internal Medicine, June 25, 2019, doi:10.1001/jamainternmed.2019.0677
  • Campbell, N.L., et al., "Preventing Alzheimer Disease by Deprescribing Anticholinergic Medications," JAMA Internal Medicine, June 25, 2019, doi:10.1001/jamainternmed.2019.0676
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Interesting.

Certainly a long list of such drugs.

The only one on the high AC activity list that I ever use is Pseudoephedrine (sudafed) when I have a cold, but that’s only once a year (average) for a few days.

It’s also interesting that I’ve always had an adverse mental reaction to two antihistamines on the lists (benadryl and claritin) and don’t use them, but I do use use allegra which isn’t on the list.

A quick side search shows that caffeine may be somewhat anti-anticholinergic (more research required) so maybe I should start drinking caffeinated tea again (or learn to like coffee – gaaaahck!). Or maybe eat even more chocolate!!!!! Yeah, more chocolate, that’s the ticket!!!!

A quick review of the literature indicates that not all studies have found a strong link between anticholinergic drugs and dementia. For example:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000871/

Cognitive slowing associated with elevated serum anticholinergic activity in older individuals is decreased by caffeine use

Excerpt:

=====
Conclusions

These results suggest that anticholinergic medications are a relatively minor contributor to the decrements in basic processing resources commonly found in studies of normal aging.

=====

My conclusion is:

Sure, when in doubt avoid medicines when possible, but I wouldn’t not take something prescribed that enhances my health and enjoyment of life now because of possible dementia later. More research required.

ACE inhibitor drugs have been measured as highly anticholinergic in some studies but most docs appear not to be aware. I saw the side effects with Captopril and Lisinopril – the ones I used and if still needed cut the doses as possible. (ARB’s were still very expensive and insurance kleptos would not cover them).

When my father in law passed away, my mother in law moved in with us and she already had some significant dementia. I began going to her doctor appointments and realized she was on 2 anticholinergic drugs. Not only that, they had been prescribed long ago, neither was doing anything for her or needed any longer, but the doctors had never thought to take her off. I got her off of them right away because I had already read about it on this site. She died of Alzheimers a few years later and we’ll never know how much those drugs contributed.

I was diagnosed with the rare Primary Progressive Multiple Sclerosis in 2011. I slowly added up symptoms as months went by. One was a loss of bladder control. I was prescribed the drug “Oxybutynin”. Quickly after, I started having cognitive problems.That is not unusual with MS however this came on quickly and I was scared. THANKS TO PEOPLE’S PHARMACY, I read their article several years ago and took myself off. Almost immediately, my cognitive problems lessened. THANK YOU PEOPLE’S PHARMACY! I also have a new doctor :)

Is Lexapro one of these drugs?

Thank you for your responses.

I’ve been on this for 4 years & cut it down to 10mg but I would like to stop taking it for GAD.

Dagny – what are first generation antihistamines?

I’m wondering about Ativan (lorazepam). It is very helpful to me, but my physician really limits the amount she will prescribe. She says it, too, has been related to Alzheimer’s. In one article it seemed to me that it leaves the body relatively quickly, reducing the concern. I take it on a rather limited basis.

In your article “Where can I find a list of anticholinergic drugs?”, Paroxetine (Paxil) is described as having low anti-cholinergic activity. Here you suggest that it has “significant anti-cholinergic effect”. Could you clarify?

Ann,
Assessing the degree of anticholinergic activity is somewhat tricky. Here are data on paroxetine from International Clinical Psychopharmacology (July, 2014):

“Thus, commonly reported adverse effects of paroxetine are symptoms of sedation, constipation, and visual disturbance, which could be ascribed to anticholinergic activity (Pae and Patkar, 2007). Indeed, paroxetine has considerable potency for muscarinic receptors, allowing it to affect these receptors at the blood levels expected during treatment (Table 2). A study in mice, in which the anticholinergic effects of paroxetine were measured using oxotremorine-induced tremor, spontaneous defecation, and passive avoidance performance tests, also supports the notion of paroxetine having anticholinergic activity in vivo (Fujishiro et al., 2002). It was found that paroxetine induced more anticholinergic effects than fluvoxamine (another SSRI), although its effects were lower than those of a tricyclic clomipramine, as expected (Fujishiro et al., 2002). In a comparative study of escitalopram and paroxetine, the anticholinergic activity was assessed as blockade of hypothermia induced by the muscarinic agonist oxotremorine (Fig. 3a). Oxotremorine caused dose-dependent hypothermia, which was prevented by paroxetine but not escitalopram (Fig. 3a), demonstrating the anticholinergic activity of paroxetine.”

Darn. I’ve been using ChlorTabs for 35 years, and it’s chlorpheniramine maleate.

Chlorpheniramine is on your list of Anticholinergic Drugs – does the “maleate” change it to something safe?

If I’m not mistaken, anticholinergic drugs include first generation antihistamines, which are available over the counter. I’ve taken these for sleep a few nights in a row and experienced memory problems for weeks afterward and headacheless migraines for a week or two as well. My yard man has been taking these drugs for years and he barely has any mind left. He can’ t remember much of anything, and apparently is not aware of it because he doesn’t write things down. I believe a few customers have chewed him out about this, but he apparently forgets that, too. I can hardly wait until he retires.

Neurontin is not mentioned on the list of drugs, but you also mention epilepsy drugs, which it is. I’m on a high dose. Am I affected?

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