Anticholinergic Medications (like Benadryl) and Dementia: Is There a Link?

Recent studies, along with viral videos circulating social media, have discussed a possible link between certain medications and dementia. These medications are called “anticholinergic drugs,” and they include antihistamines like Benadryl®, as well as medicines for other conditions. It has been suggested that long-term use of anticholinergics or medications with anticholinergic effects can increase the chances of developing dementia. 

Benadryl® and some other antihistamines contain diphenhydramine, which is used to treat symptoms caused by allergies, hay fever and colds. Diphenhydramine can be found over the counter in other “first-generation” allergy products (sometimes called “drowsy antihistamines,” in contrast to non-drowsy options), as well as in medications used for sleep or for motion sickness, such as Zzzquil™, Unisom® and Dramamine®. 

What is Dementia? 

According to the Alzheimer’s Association, dementia is “a general term for loss of memory, language, problem-solving and other thinking abilities that are severe enough to interfere with daily life.” Damage to brain cells that prevent communication between each other will cause a decline in different functions of the body such as memory and decision making, depending on which area of the brain is affected.  

Dementia most commonly affects adults 65 and older. Alzheimer’s disease is the most common form of dementia and accounts for 60 to 80 percent of all dementia cases. As of March 2023, more than 55 million people worldwide have a form of dementia. In the U.S., it is the fifth leading cause of death in people 65 and older.  

What Causes Dementia? 

Age, race, family history, heart health and head injuries are risk factors in developing dementia. Lifestyle choices such as alcohol consumption, eating a poor diet and smoking, as well as environmental factors like pollution and pesticide exposure have also been linked to an increased risk of dementia. With several published case studies addressing anticholinergic drug exposure and dementia risk since 2015, anticholinergic medication usage can also be added to the list of factors that may impact developing dementia. 

Julie Livesay, APN, nurse practitioner at Crossville Medical Group, says that age is the biggest risk factor for dementia. While age isn’t controllable, she adds that taking steps such as getting regular physical activity, not smoking, eating a healthy diet, maintaining a healthy blood pressure, and controlling cholesterol and blood sugar are key lifestyle factors for decreasing your dementia risk. 

What are Anticholinergic Drugs? 

Anticholinergic medications are used to treat a variety of conditions, including chronic obstructive pulmonary disease, Parkinson’s disease, depression and overactive bladder conditions. Some older antihistamines and tricyclic antidepressants, along with over-the-counter medications frequently used as sleep aids or to help with motion sickness also have anticholinergic properties. 

What do Anticholinergic Drugs Do to Our Brains? 

Anticholinergic drugs block the activity of the neurotransmitter acetylcholine, which delivers messages from one nerve cell to another in various areas of the body. It plays a large role in muscle movement, as well as heart rate, blood pressure, urination, digestion, memory and attention. By blocking these neurotransmitters, anticholinergic drugs inhibit nerve impulses responsible for these bodily functions. 

Do Anticholinergic Medications Cause Dementia? 

While there is no definitive evidence that anticholinergic medications cause dementia, observational studies have indicated that long-term use can increase the risk of dementia or mild cognitive impairment.  

A 2015 study published in JAMA Internal Medicine (Journal of the American Medical Association) found that individuals 65 years and older taking an anticholinergic daily for more than three years had an increased risk of developing dementia. A similar 2019 study researched the effects of anticholinergic medications on adults 55 years and older and found the most significant increases were associated with specific anticholinergics: antidepressants, bladder antimuscarinics, antipsychotics and antiepileptic drugs. 

However, a 2023 study published in the Alzheimer’s Disease & Associated Disorders Journal found that there was no conclusive link of anticholinergics increasing the risk of dementia, but there was a significant association with a higher risk of developing mild cognitive impairment. Mild cognitive impairments can affect memory, but typically do not interfere with day-to-day life like dementia. Evidence did not suggest a connection between a higher amount of anticholinergics and an increased likelihood of developing mild cognitive impairment. 

Livesay encourages people to be familiar with the different medications that can increase the risk of dementia. “Older antihistamines, sleep medications, antipsychotics, some controlled substances and narcotics can increase the risk of dementia,” she said. “If patients have been on this class of medications long-term, it is essential that doses are decreased or discontinued if at all possible as we age.” 

Who Should Avoid Anticholinergics? 

Studies recommend that older adults should avoid using anticholinergics, as older people may be more susceptible to unwanted side effects than younger people. Those with dementia or Alzheimer’s should find alternative medications if treating a condition typically treated with anticholinergics. 

All adults should refrain from long-term use of these medications and find safer alternatives for allergy medications and sleep aids. If a medication contains diphenhydraminie, consider an alternative option. 

Do Other Antihistamines Cause Dementia? 

Over-the-counter non-drowsy antihistamines (examples include Claritin®, Zyrtec® and Allegra®) do not have anticholinergic effects, which may make them safer options for treating allergy symptoms long-term, particularly among older adults.  

Safer Sleep-Aid Alternatives 

Since some over-the-counter sleep aids have anticholinergic effects, it’s important to find alternatives when possible.  

Melatonin is a naturally occurring hormone that the brain produces in response to darkness to aid with the circadian rhythm and sleep. It can also be taken as a supplement to assist with sleep disorders like insomnia and to promote falling asleep sooner.  

Additionally, a sleep study can help identify whether poor sleep is the result of a health condition like restless leg syndrome or sleep apnea. Lifestyle adjustments such as limiting caffeine, having a regular nighttime routine and limiting screen time before bed also can support a better night’s rest.  

Covenant Health has sleep centers across the region to help diagnose and treat sleep disorders. More resources about improving sleep are available below: 

• Five Tips for Better Sleep 
• Sleep Success for Older Adults 
• Sleep Debt and Sleep Deprivation 

The Future of Dementia Treatment

Ultimately, more research is still needed to conclusively determine the long-term effects of anticholinergics. Luckily, research into treatment options and medications that can slow the effects of dementia and Alzheimer’s disease is ongoing.

Livesay encourages people to stay in the loop about new dementia research. “New information comes out all the time regarding dementia. Discuss new findings with your medical provider as it becomes available.” 

Speak to your primary care provider if you have a concern about anticholinergic medications or other risk factors for dementia. Find a primary care provider near you.