Common medications may be linked to increased dementia risk

Anticholinergics are among one of the most common types of drugs prescribed. It’s not known how frequently they’re prescribed; different studies have found the number to be between 11 and 80 percent in older populations. But research is raising concerns about their safety.

A 2021 systematic review published in Neuroscience and Biobehavioral Reviews found that one risk factor for dementia and Alzheimer’s disease is the use of anticholinergic drugs. And the more exposure a person has to these medications, the higher their risk of developing dementia.

What are anticholinergic drugs?

Anticholinergics are medicines that are used for a variety of conditions that affect mental health and the neurologic, respiratory, ophthalmic, and urological systems in the body. People take anticholinergics to treat many health issues, including depression, Parkinson’s, urinary incontinence, gastrointestinal disorders, and allergies.

Some anticholinergics work by preventing the neurotransmitter acetylcholine (also known as the cholinergic system) from sending messages through the nervous system. Some drugs do this on purpose, while others block acetylcholine and suppress the cholinergic system as an unintended side effect.

Acetylcholine is involved in the production of memory and other aspects of cognition, and it’s one of the neurotransmitters that becomes depleted rapidly during the onset of Alzheimer’s disease and related forms of dementia. (Acetylcholine levels also drop, but to a much lesser extent as a result of natural aging.) It’s worth noting that many drugs used today to treat Alzheimer’s work by increasing the activity of acetylcholine.

Healthcare providers (HCPs) tend to think in terms of anticholinergic burden (ACB), which refers to the overall effect over time of taking any medications that involve these neurotransmitter blocks. Your HCP will be able to look at all the medications you regularly take and calculate how big of a load of anticholinergics you are taking and discuss alternative medications with you that have less cognitive risk associated with them.

What is dementia?

Dementia is a general term that describes symptoms associated with a decline in mental ability. The most common cause of dementia in people 65 and older is Alzheimer’s disease, which involves the formation of clumps of protein in the brain that are believed to interfere with the ability of brain cells to communicate with each other.

Dementia often entails impaired memory, as well as altered language abilities, confusion and disorientation, difficulty paying attention, hampered judgment, personality changes, and problems with motor function. These symptoms tend to start slowly and get worse over time.

To diagnose dementia, an HCP will typically analyze a patient’s medical history, perform a physical exam and cognitive and neurological tests, and ask the patient and loved ones about changes in cognition, behavior, and daily function.

Do anticholinergics increase dementia risk?

The authors of the 2021 systematic review found that people who take anticholinergic drugs for the treatment of Parkinson’s disease, bladder issues, and depression are most at risk. Drugs for Parkinson’s were associated with a 39 percent higher risk of dementia, and urological drugs and antidepressants increased the risk by 27 percent and 19 percent, respectively. And the higher the drug burden, the higher the risk.

They also found that there wasn’t enough evidence to show a strong link between dementia and anticholinergic drugs designed to treat psychosis, pain, or respiratory issues. And anticholinergic drugs that treat gastrointestinal and cardiovascular health issues may even offer a tiny bit of lowered dementia risk. The authors theorized that this could be because these drugs protect the person taking them from other dementia risk factors, like hypertension and depression.

It’s important to note that much more research needs to be done to really understand the complex relationships between the body and these drugs.

What about antihistamines?

First-generation antihistamines like diphenhydramine (Benadryl) have a high anticholinergic burden compared to second-generation antihistamines like loratadine (Claritin). So far, only a tiny amount of research has been done, and it’s found some association between anticholinergic antihistamines and higher dementia risk. As with other anticholinergics, more research is needed to understand the effects, if any, that antihistamines may have on dementia risk.

If I’m taking an anticholinergic, should I stop?

Older adults and people who already have dementia should avoid anticholinergics if possible. However, the review authors noted that the approach to medications should be like balancing a teeter-totter, with the benefits of some drugs outweighing their risks in some cases.

"My suggestion is: Anytime your doctor gives you medicine, first ask, ‘What are the potential adverse effects of this medicine on my brain health?’” says Malaz Boustani, MD, a research scientist at the Indiana University Center for Aging Research. “Demand time with your doctor to explain to you the risks and benefits of anticholinergics, including over-the-counter drugs. If your doctor doesn’t have that time, find a doctor that does.”

While you shouldn’t abruptly stop taking drugs you need without checking with an HCP, there may be alternatives to anticholinergics for your condition. For example, SSRIs other than paroxetine may be smart alternatives to tricyclic antidepressants for people with depression, and both people with depression and bladder control issues may benefit from non-drug treatments such as cognitive behavioral therapy.

“There aren’t many risk factors for Alzheimer’s disease that are easy to modify,” says Dr. Boustani. “For example, it can be hard to change your diet and exercise habits, but it can be relatively easy to stop taking anticholinergic medications.”

Boustani’s recommendation? “If you already have risk factors, such as a first-degree relative with Alzheimer’s disease, don’t tip it over by taking anticholinergics.”