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

Many people over 65 take medications like Benadryl for allergies, oxybutynin for overactive bladder, or amitriptyline for nerve pain or depression. These drugs work well for their intended purposes-but what they don’t tell you on the label could be quietly affecting your brain. Growing evidence shows that long-term use of anticholinergic medications may increase the risk of dementia, even in people who show no signs of memory problems yet.

What Are Anticholinergic Medications?

Anticholinergic drugs block acetylcholine, a chemical in your brain and body that helps with memory, muscle control, digestion, and sleep. These medications were developed decades ago and are still widely used today. Common ones include:

• Diphenhydramine (Benadryl, Tylenol PM) - for allergies and sleep
• Oxybutynin (Ditropan) and Solifenacin (Vesicare) - for overactive bladder
• Amitriptyline (Elavil) - for depression and chronic pain
• Chlorpheniramine - in many cold and flu remedies
• Hyoscine - for motion sickness

There are about 100 of these drugs available, both by prescription and over the counter. What makes them dangerous over time isn’t the short-term use-it’s the cumulative exposure. Studies show that taking these medications for months or years can lead to measurable changes in the brain.

The Link Between Anticholinergics and Dementia

A 2019 study using data from over 3,400 older adults found that people who took medications with high anticholinergic activity for three years or more had a 49% higher risk of developing dementia compared to those who didn’t take them. The risk didn’t jump overnight-it climbed steadily with each extra dose.

Brain scans from the Alzheimer’s Disease Neuroimaging Initiative revealed something alarming: long-term users showed 0.5% to 1.2% more brain volume loss each year in areas like the hippocampus and amygdala-regions critical for memory. Their brains also used 4% to 8% less glucose, a sign of reduced activity. These aren’t subtle changes. They’re the kind of damage seen in early Alzheimer’s.

Not all anticholinergics are created equal. Tricyclic antidepressants like amitriptyline carried the highest risk (29% increased dementia odds), followed by bladder drugs like oxybutynin (23% increase) and antipsychotics. But some drugs in the same class, like trospium for bladder issues, showed no increased risk. Why? Because they don’t cross the blood-brain barrier as easily. That’s why the type of drug matters as much as the dose.

How Much Is Too Much?

Researchers use a tool called the Anticholinergic Cognitive Burden (ACB) scale to rate drugs from 0 (no effect) to 3 (strong effect). A score of 3 means the drug has a major impact on the brain. If you’re taking multiple drugs with scores of 1 or 2, those add up.

One study found that people who took a total of 1,095 daily doses over time-roughly three years of one daily pill-had nearly double the dementia risk. That’s not a huge number. It’s less than one pill a day for three years. Many people don’t realize they’re hitting that threshold because they’re taking over-the-counter meds on top of prescriptions.

For example: someone on amitriptyline (ACB=3) for depression, diphenhydramine (ACB=3) for sleep, and oxybutynin (ACB=3) for bladder control is already at a cumulative score of 9. That’s not rare. It’s common. And it’s dangerous.

Who’s Most at Risk?

It’s not just older adults. People in their 50s and 60s who’ve been on these drugs for a decade are now showing up with memory complaints. The risk is highest for those who:

• Take more than one anticholinergic at a time
• Use them for three years or longer
• Have the APOE-ε4 gene (a genetic risk factor for Alzheimer’s)
• Already have mild memory problems

But here’s the thing: you don’t need to be diagnosed with anything to be at risk. These drugs can quietly erode cognitive function before you notice it. One woman in her late 60s, on amitriptyline for eight years, saw her MMSE score drop from 28 (normal) to 22 (mild impairment). After stopping the drug, her score stabilized-but never returned to what it was.

What Doctors Aren’t Telling You

Despite the evidence, only 37% of primary care doctors routinely check for anticholinergic burden in patients over 65. Many still believe these drugs are harmless short-term fixes. But the American Geriatrics Society’s Beers Criteria® has warned since 2019: avoid strong anticholinergics in older adults. The European Medicines Agency restricted seven bladder drugs for elderly use in 2021. The FDA added stronger warnings to 14 anticholinergic medications in 2020.

Yet patient leaflets? Only 42% mention cognitive risks-even though EU law requires it. Most people don’t know their sleep aid or bladder pill could be harming their brain. And when they do, they’re often told, “It’s just a side effect-it’ll go away.” But research shows: it doesn’t always.

Alternatives That Work

You don’t have to live with symptoms just to avoid dementia. Safer options exist for nearly every condition:

• For overactive bladder: Switch from oxybutynin to mirabegron (Myrbetriq). It works just as well, has an ACB score of 0, and doesn’t cross into the brain.
• For depression or anxiety: Try an SSRI like sertraline or escitalopram instead of amitriptyline. You lose the brain fog and gain better long-term outcomes.
• For insomnia: Skip diphenhydramine. Try cognitive behavioral therapy for insomnia (CBT-I)-it’s more effective long-term and has no side effects.
• For allergies: Use non-sedating antihistamines like loratadine (Claritin) or cetirizine (Zyrtec). They’re just as effective and have no anticholinergic activity.

These aren’t experimental. They’re standard, approved, and widely available. The only barrier? Awareness.

What You Can Do Now

If you or a loved one is taking one or more of these drugs, here’s what to do:

1. Make a list of every medication you take-including supplements and OTC pills.
2. Check the ACB score using free online tools from the University of Eastern Finland or ask your pharmacist.
3. Don’t stop cold turkey. Some drugs, like antidepressants, need to be tapered slowly to avoid withdrawal.
4. Ask your doctor: “Is this drug necessary? Is there a non-anticholinergic alternative?”
5. Track changes. Note any memory lapses, confusion, or trouble focusing before and after switching meds.

One woman in Manchester replaced her nightly Benadryl with melatonin and a strict bedtime routine. Within six weeks, she stopped forgetting where she put her keys. “I didn’t realize I’d been foggy for years,” she said.

The Bigger Picture

Experts estimate that reducing anticholinergic use could prevent up to 15% of dementia cases each year-that’s over half a million people globally. This isn’t just about individual pills. It’s about a system that prioritizes symptom relief over long-term brain health.

Research is moving fast. The PREPARE trial, currently enrolling 3,000 people at risk for Alzheimer’s, is testing whether stopping these drugs can delay or prevent dementia. Meanwhile, seven new bladder drugs and three antidepressants in Phase III trials are being designed to avoid brain penetration entirely.

The message is clear: if you’re taking an anticholinergic drug long-term, it’s time to ask questions. Your brain is worth it.