Millions of people take prescription and over-the-counter medications every day without giving much thought to how those medicines might affect the brain over the long term.
But researchers have been paying particular attention to a group of medications known as anticholinergic drugs.
These medicines block the action of acetylcholine, a chemical messenger involved in functions including memory and learning. Anticholinergic medicines are used for a wide range of conditions, from allergies and bladder problems to depression and Parkinson’s symptoms.
Research supported by the National Institute on Aging has found an association between greater cumulative exposure to strong anticholinergic medicines and a higher incidence of dementia in older adults. However, an association does not prove that these medicines directly cause dementia, and underlying health conditions can complicate the relationship.
Here are eight types of medication worth discussing with your doctor or pharmacist—particularly if you are older or take several medicines.
- Some
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- Older Antidepressants
Certain older antidepressants, particularly some tricyclic antidepressants, have strong anticholinergic effects.
Examples include medications such as amitriptyline and paroxetine, although anticholinergic activity varies substantially between antidepressants.
A large case-control study involving more than 280,000 people found that greater cumulative exposure to strongly anticholinergic antidepressants was associated with higher odds of dementia.
This does not mean antidepressants in general cause dementia.
Depression itself can be associated with dementia risk and may sometimes precede a dementia diagnosis, making the relationship difficult to untangle.
If you take an antidepressant, do not stop it suddenly. Ask your healthcare provider whether your medication has significant anticholinergic effects and whether it remains the most appropriate choice for you.
- Some Overactive Bladder Medications
Medications used for an overactive bladder are among the most closely studied anticholinergic drugs.
Examples of antimuscarinic bladder medicines include oxybutynin, tolterodine and solifenacin.
A 2019 study found that high cumulative
- exposure to bladder antimuscarinic medications was associated with increased odds of dementia.
Another population study comparing people starting anticholinergic bladder medications with those starting the non-anticholinergic beta-3 agonist mirabegron found a higher dementia incidence among the anticholinergic group.
However, newer research illustrates why caution is necessary when interpreting these results. A large Danish study found an association when anticholinergic bladder drugs were compared with non-use, but that increase was not observed when they were directly compared with mirabegron users. The researchers highlighted how the choice of comparison group can substantially affect the apparent relationship.
- First-Generation Antihistamines
Some older antihistamines used for allergies and sleep have strong anticholinergic effects.
Diphenhydramine, for example, is found in some allergy medicines and over-the-counter nighttime sleep products.
First-generation antihistamines were among the most commonly used strong anticholinergic medication classes in a long-term study of adults aged 65 and older. That study found a dose-response relationship
- between overall cumulative strong-anticholinergic exposure and dementia incidence.
That doesn’t establish that an occasional antihistamine dose causes dementia.
The concern is more relevant to repeated or long-term exposure, particularly in older adults or people taking several anticholinergic medicines.
- Some Parkinson’s Disease Medications
Certain medicines used to manage Parkinson’s symptoms have anticholinergic activity.
One large study found that high cumulative exposure to strongly anticholinergic antiparkinson medications was associated with higher odds of dementia.
This relationship is particularly difficult to interpret because Parkinson’s disease itself can cause cognitive impairment and dementia.
That makes it inappropriate to conclude simply that the medication caused the dementia.
For people with Parkinson’s disease, treatment decisions should be individualized with a neurologist or other qualified healthcare professional.
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- Some Antipsychotic Medications
Certain antipsychotic medicines also have anticholinergic properties.
The 2019 case-control study found an association between high cumulative exposure to strongly anticholinergic antipsychotic medications and dementia.
But once
- again, there is an important complication: the medical conditions for which these drugs are prescribed can themselves be related to cognitive health.
Other research has produced more complicated findings and emphasizes that underlying illness and prescribing choices can confound the apparent relationship between anticholinergic burden and cognitive outcomes.
Antipsychotics should therefore never be stopped or altered without medical supervision.
- Some Anti-Seizure Medications
Some medications used to control seizures can contribute to anticholinergic burden.
In the large 2019 study, high cumulative exposure to strongly anticholinergic antiepileptic medicines was associated with increased odds of dementia.
That finding should not be interpreted to mean that seizure medicines generally cause dementia.
Epilepsy and other neurological conditions can themselves affect cognition, and different anti-seizure medications have very different pharmacological properties.
Abruptly stopping certain seizure medications can also be dangerous.
- Some Medications Used for Nausea, Dizziness or Motion Sickness
Certain medicines used for nausea, vertigo or
- motion sickness have anticholinergic effects.
This matters because people may not realize that medications prescribed for very different problems can all contribute to their total anticholinergic burden.
Research suggests that cumulative exposure may be important. In one prospective study of adults aged 65 and older, participants with the highest cumulative exposure to strong anticholinergics had a higher rate of incident dementia than non-users.
Rather than focusing on a single pill, a medication review can help identify the combined anticholinergic effects of everything a person takes.
- Some Over-the-Counter Sleep Aids
This category can easily be overlooked.
Some nighttime sleep products contain older sedating antihistamines with anticholinergic properties.
Because they’re available without a prescription, people may assume they’re harmless for regular long-term use.
The National Institute on Aging specifically notes that some anticholinergic medicines are available over the counter and are commonly used as sleep aids. These medicines can impair cognition, particularly
- in older people.
If you’re regularly relying on an OTC sleep aid, tell your doctor or pharmacist exactly which product you’re using.
Why Are Anticholinergic Drugs a Concern?
Acetylcholine plays an important role in the nervous system, including functions related to learning and memory.
Anticholinergic medicines reduce acetylcholine activity.
Short-term cognitive effects of these medications have been recognized for years, particularly among older adults. The bigger question has been whether substantial exposure over many years might also be associated with persistent cognitive problems or dementia.
A systematic review and meta-analysis combining 14 longitudinal and case-control studies involving more than 1.5 million participants found anticholinergic use was associated with higher risks of all-cause dementia and Alzheimer’s disease, with evidence of a dose-related relationship.
But observational studies have an important limitation:
Association is not the same as causation.
People taking these medicines may have medical conditions that themselves influence dementia risk.
- Some medications may even be prescribed for symptoms that represent very early stages of an illness that has not yet been diagnosed.
Researchers therefore continue to investigate how much of the observed relationship is caused by the drugs themselves.
Does Taking One of These Medicines Mean You’ll Develop Dementia?
No.
Finding an association at the population level doesn’t mean an individual taking one of these medications will develop dementia.
Risk may depend on factors including:
The particular medication and its anticholinergic strength
Dose and duration of use
Total exposure over time
Age
Other medications being taken
Existing medical conditions
Individual dementia risk factorsResearch has repeatedly suggested that greater cumulative exposure deserves particular attention.
Don’t Suddenly Stop Your Medication
This is perhaps the most important message in this article.
Do not stop a prescription medication simply because you see its name or drug class on a list like this.
Suddenly
- stopping antidepressants, seizure medicines, Parkinson’s treatments, psychiatric medications, or other prescription drugs can cause serious problems.
Instead, ask a doctor or pharmacist for a medication review.
You can ask:
“Do any of my medicines have strong anticholinergic effects, and is there an appropriate alternative with a lower anticholinergic burden?”
Your healthcare professional can consider the benefits of the medicine, your medical history, dose, duration of treatment, other medications and possible alternatives.
The Bottom Line
Researchers have found associations between long-term cumulative exposure to certain strong anticholinergic medicines and a higher incidence of dementia, particularly for some antidepressant, bladder, antiparkinson and other medication classes.
That does not mean these medicines have been proven to directly cause dementia, nor does it mean everyone taking them is in danger.
The practical message is much simpler:
If you’re older, take multiple medications, or have been using an anticholinergic medicine for a long time, it
- may be worth asking your doctor or pharmacist to review your medications.
Don’t stop prescribed medication on your own.
Medical disclaimer: This article is for general educational purposes only. It does not provide a diagnosis or replace individualized medical advice from a physician or pharmacist. Never stop, start, or change the dose of prescription medication without appropriate medical guidance.
