Anticholinergic Medications and Dementia: What You Need to Know About Cognitive Risk

Many people over 65 take medications for common issues like allergies, overactive bladder, depression, or insomnia. What they might not realize is that some of these everyday pills could be quietly harming their brain. A growing body of research shows that long-term use of anticholinergic medications is linked to a higher risk of dementia and measurable cognitive decline-even in people who seem fine at first.

What Are Anticholinergic Medications?

Anticholinergic drugs work by blocking acetylcholine, a chemical in your brain and body that helps with memory, muscle control, and many automatic functions like digestion and bladder control. These medications have been around for decades and are still widely prescribed. Common ones include diphenhydramine (Benadryl), oxybutynin (Ditropan), amitriptyline (Elavil), and hydroxyzine (Vistaril).

You’ll find them in both prescription and over-the-counter forms. For example, many sleep aids and allergy pills contain diphenhydramine. People take them for everything from hay fever to urinary urgency to chronic pain. But the problem isn’t just taking one pill now and then. It’s the long-term, daily use that adds up.

The Link to Dementia Is Real-And Measurable

Studies tracking tens of thousands of older adults over years have found a clear pattern: the more anticholinergic drugs someone takes, and the longer they take them, the higher their risk of dementia. One major study from the French National Health Insurance database looked at over 1,000 people and found that those who took the equivalent of 1,095 daily doses or more over several years had a 49% higher risk of developing dementia compared to those who didn’t take any.

It’s not just about memory loss. Brain scans show that long-term users have faster shrinkage in areas like the hippocampus-the part of the brain responsible for forming new memories. Glucose metabolism in the brain also drops by 4-8% in these individuals, meaning their brain cells aren’t getting enough energy to function properly.

These aren’t temporary side effects like drowsiness or dry mouth. This is structural, lasting damage. One study found that people on high-anticholinergic drugs lost 0.5-1.2% more brain volume per year than those not taking them. That’s the same rate of decline seen in early Alzheimer’s disease.

Not All Anticholinergics Are Created Equal

Some drugs in this class are far more dangerous than others. The risk isn’t the same across the board. According to research published in JAMA Internal Medicine, antidepressants like amitriptyline carry the highest risk, with a 29% increased chance of dementia. Antipsychotics come next, then bladder medications like oxybutynin and solifenacin.

But here’s something important: trospium, another drug used for overactive bladder, showed no significant link to dementia in the same study. Why? Because it doesn’t cross the blood-brain barrier as easily. That’s a key difference. Drugs that stay mostly outside the brain-like glycopyrrolate or trospium-pose much less risk than those that get inside, like doxepin or amitriptyline.

This means you can’t just say, “All anticholinergics are bad.” You have to look at the specific drug, its strength, and how much of it crosses into the brain. The Anticholinergic Cognitive Burden (ACB) scale helps doctors rate this, with scores of 3 meaning high risk, 2 meaning moderate, and 1 meaning low.

Who’s Most at Risk?

Older adults are the main group affected, but it’s not just age. People who take multiple anticholinergic drugs at once-say, one for sleep, one for bladder control, and one for depression-are at the highest risk. The effects stack up. One pill might not do much. But three or four? That’s when the brain starts to pay the price.

People with a family history of Alzheimer’s or those who carry the APOE-ε4 gene variant are especially vulnerable. That’s why researchers are now running trials like the PREPARE study, which is testing whether stopping these drugs early in high-risk individuals can slow or prevent dementia.

And it’s not just seniors. People in their 50s and 60s who’ve been on these meds for 5-10 years are now showing up with mild cognitive issues. Many don’t connect the dots until it’s too late.

What Patients Are Saying

Real people are seeing the effects. On patient forums, stories like this come up often: “My mom was on amitriptyline for nerve pain for eight years. Her memory got worse. When she stopped it, things didn’t get better-but they didn’t get worse either.”

Others report improvements after switching. One woman switched from oxybutynin to mirabegron for her overactive bladder. Within months, she said she could think more clearly, remember names better, and didn’t feel so foggy in the afternoons.

But here’s the problem: most patients don’t know these drugs can affect their brain. A 2021 survey found that only 37% of primary care doctors routinely check for anticholinergic burden in patients over 65-even though nearly 90% of them agree it’s a risk in theory.

And many patients don’t report cognitive side effects because they assume forgetfulness is just “getting older.” Drugs.com reviews show that only 22% of people taking oxybutynin mention brain fog, even though it’s a known side effect.

What Can You Do?

If you’re on any of these medications, don’t stop cold turkey. Some can cause withdrawal symptoms like increased heart rate, sweating, or even confusion. But you can take action:

1. Ask your doctor for a full medication review. Bring in every pill, supplement, and OTC product you take. Ask: “Is this anticholinergic? What’s the ACB score?”
2. Look for safer alternatives. For depression, SSRIs like sertraline or escitalopram have little to no anticholinergic effect. For overactive bladder, mirabegron is a good option. For insomnia, cognitive behavioral therapy (CBT-I) works better than sleeping pills long-term.
3. Check your OTC meds. Benadryl, Unisom, and many “PM” pain relievers contain diphenhydramine. Switch to non-sedating antihistamines like loratadine or cetirizine.
4. Use the ACB scale. You can find free online calculators from the University of Eastern Finland. Plug in your meds and see your total score. A score of 3 or higher is a red flag.

The American Geriatrics Society’s Beers Criteria already lists strong anticholinergics as drugs to avoid in older adults. But awareness is still low. That’s why the Anticholinergic Risk Reduction Initiative aims to cut inappropriate prescribing by 50% by 2027.

What’s Changing in 2025?

Regulators are catching up. The FDA added stronger dementia warnings to 14 anticholinergic drugs in 2020. The European Medicines Agency restricted seven bladder drugs for elderly use in 2021. But patient leaflets still often don’t mention cognitive risks-only 42% of them do, even though EU law requires it.

Meanwhile, drug companies are responding. As of 2023, seven new bladder treatments and three new antidepressants are in late-stage trials-all designed to avoid crossing into the brain. These aren’t just incremental improvements. They’re a shift in design philosophy: treat the condition without hurting the mind.

Experts estimate that reducing anticholinergic exposure could prevent 10-15% of dementia cases each year. That’s over half a million people worldwide who might avoid cognitive decline if we act now.

It’s Not About Fear-It’s About Awareness

No one is saying you can’t take these medications if you need them. Some people rely on them for severe pain, incontinence, or depression that hasn’t responded to anything else. The goal isn’t to scare you. It’s to make sure you know the trade-offs.

If you’ve been on an anticholinergic drug for more than a year, especially if you’re over 60, it’s worth asking: “Is this still the best option?”

Your brain doesn’t always tell you when it’s under stress. But the science is clear: long-term use of these drugs can accelerate cognitive decline. And unlike some other dementia risks-like genetics-you can do something about this one.

Next Steps for Patients and Caregivers

If you’re worried about your meds:

• Make a list of everything you take-prescription, OTC, and supplements.
• Use the ACB scale calculator to get your total burden score.
• Book an appointment with your doctor or pharmacist to review each drug.
• Ask: “Is there a non-anticholinergic alternative?”
• If you’re switching, do it slowly. Withdrawal can cause symptoms if stopped too fast.

Don’t wait until you’re forgetting names or getting lost in familiar places. The brain changes silently. But you don’t have to accept it as normal aging. Knowledge is your best tool-and action, even small steps, can make a real difference.