Anticholinergic Burden in Older Adults: How Common Medications Raise Dementia Risk

Many older adults take medications every day to manage pain, allergies, bladder issues, or depression. But what if some of those pills are quietly harming their brains? The truth is, a growing body of research shows that anticholinergic burden-the combined effect of multiple drugs that block acetylcholine-is one of the most preventable causes of cognitive decline in seniors. And it’s happening far more often than most people realize.

What Is Anticholinergic Burden?

Anticholinergic burden refers to the total impact of medications that block acetylcholine, a key chemical in the brain that helps with memory, attention, and learning. These drugs don’t just affect the body-they cross into the brain and interfere with brain circuits that control thinking. The more of these drugs someone takes, and the longer they take them, the greater the risk.

There are three main scales doctors use to measure this burden: the Anticholinergic Cognitive Burden (ACB) scale, the Anticholinergic Risk Scale (ARS), and the Drug Burden Index (DBI). The ACB scale is the most widely used today. It rates each medication from Level 1 (mild) to Level 3 (strong). A person taking two Level 2 drugs and one Level 3 drug might have an ACB score of 7. That’s considered high. And high scores are linked to real brain changes.

How These Drugs Damage the Brain

Acetylcholine is especially important in three brain areas: the hippocampus (memory), the cerebral cortex (thinking), and the neostriatum (movement and planning). When anticholinergics block these receptors, brain cells can’t communicate properly. Over time, this leads to measurable damage.

A 2016 study in JAMA Neurology found that older adults taking even moderate amounts of these drugs had a 4% drop in glucose metabolism in brain regions affected by Alzheimer’s. That’s the same area that lights up in scans of people with early dementia. Another study tracked 451 seniors over three years and found those on anticholinergics lost brain volume 0.24% faster per year than those who weren’t. That may sound small, but over five years, it adds up to a noticeable difference in thinking ability.

These aren’t just lab findings. Brain imaging studies show that the longer someone takes these drugs, the more their brain activity slows down. In one large trial of nearly 20,000 people over 70, those with higher ACB scores had worse scores on memory and word-finding tests every year-even if they started out cognitively normal.

Which Medications Carry the Highest Risk?

Not all anticholinergics are the same. Some are stronger than others. The most common culprits in older adults include:

• First-generation antihistamines: Diphenhydramine (Benadryl, Tylenol PM, Advil PM) - used for allergies or sleep. This is the #1 source of high ACB scores.
• Overactive bladder drugs: Oxybutynin (Ditropan), tolterodine, solifenacin - prescribed to reduce frequent urination.
• Tricyclic antidepressants: Amitriptyline, nortriptyline - older antidepressants still used despite newer, safer options.
• Some anti-nausea and motion sickness drugs: Dimenhydrinate (Dramamine), promethazine.
• Antipsychotics: Chlorpromazine, quetiapine - sometimes used off-label for sleep or agitation in dementia.

According to 2023 prescription data, about 18% of high-ACB prescriptions in the U.S. come from diphenhydramine alone. That’s one pill many seniors take without realizing it’s dangerous. Oxybutynin and amitriptyline follow closely behind. Even though newer versions of these drugs (like solifenacin) have less brain penetration, many doctors still prescribe the older, stronger forms.

Cognitive Effects: What Gets Worse?

The damage isn’t random. Anticholinergics hit certain brain functions harder than others.

• Executive function - planning, organizing, switching tasks - drops the most. In the ASPREE study, each point increase in ACB score led to a 0.15-point annual decline on word association tests.
• Episodic memory - remembering recent events or conversations - also declines significantly. Each ACB point meant a 0.08-point drop per year on memory recall tests.
• Processing speed - how fast someone thinks or reacts - shows the weakest link. Some studies found no real effect.

This means seniors might not forget names right away, but they’ll struggle to follow a conversation, keep track of appointments, or manage their medications. They might seem “slow” or “confused,” but it’s not dementia yet-it’s drug-induced brain fog.

Long-Term Use = Higher Dementia Risk

It’s not just about feeling foggy today. The real danger is what happens over years.

A landmark 2015 study from the University of Washington tracked over 3,400 seniors for more than a decade. Those who took anticholinergics for three years or more had a 54% higher chance of developing dementia than those who used them for less than three months. Even after adjusting for other health conditions, the link held strong.

The American Geriatrics Society’s 2023 Beers Criteria now explicitly says: Avoid strong anticholinergics in older adults. They list diphenhydramine, oxybutynin, and amitriptyline as drugs that should be replaced if possible.

And it’s not just observational data. In the DICE trial, 286 older adults with high ACB scores had their medications carefully reviewed and reduced. After 12 weeks, their Mini-Mental State Exam (MMSE) scores improved by 0.82 points on average. That’s a measurable jump in thinking ability-enough to help someone remember to take their pills or find their way home.

Real Stories: When Stopping the Drug Changed Everything

Behind the numbers are real people.

On AgingCare.com, a caregiver named Jen wrote: “My mom was confused all the time. She’d forget where she put her keys, get lost in her own house. We thought it was early dementia. Then we found out she’d been on oxybutynin for two years. We stopped it. Two weeks later, she was back to herself. Her doctor didn’t even know it could cause this.”

The FDA’s adverse event database recorded over 1,200 cases of confusion, memory loss, or delirium linked to anticholinergics in seniors between 2018 and 2022. Most of these cases happened with drugs that were never labeled as “cognitive risks.”

A 2021 survey by the National Council on Aging found that 63% of older adults were never told about these risks when their prescriptions were written. And 41% said they’d have chosen a different treatment if they’d known.

Why Do Doctors Keep Prescribing Them?

It’s not that doctors don’t know. They do. But there are barriers.

First, many of these drugs are cheap, widely available, and easy to prescribe. Oxybutynin treats overactive bladder quickly. Diphenhydramine helps with sleep. Amitriptyline helps with nerve pain. And for many doctors, it’s the first option they reach for.

Second, switching isn’t simple. Replacing a drug means finding an alternative that works just as well. For bladder issues, mirabegron (Myrbetriq) is a non-anticholinergic option. For depression, SSRIs like sertraline or citalopram have far less brain impact. For allergies, loratadine (Claritin) or cetirizine (Zyrtec) are safer.

Third, time is tight. A 2021 survey of over 1,200 family doctors found that reviewing all medications for anticholinergic risk takes an average of 23 minutes per patient. Most appointments are 15 minutes. Only 37% of doctors felt they had enough time to do it right.

Even when high-risk prescriptions are flagged, they’re rarely acted on. One study found that only 39% of nursing home residents with high ACB scores had their meds reviewed within three months of being identified.

What Can You Do?

If you or a loved one is over 65 and taking any of these medications, here’s what to do:

1. Make a full list of every pill, patch, cream, or supplement you take-even over-the-counter ones.
2. Check the ACB scale - the American Geriatrics Society now has a free mobile app called the ACB Calculator. Just enter the drug names and it gives you a score.
3. Ask your doctor: “Is this drug anticholinergic? Is there a safer alternative?” Don’t be afraid to say, “I’ve read this might affect my memory.”
4. Don’t stop cold - some drugs need to be tapered. Ask for a plan.
5. Give it time - cognitive improvement can take 4 to 8 weeks after stopping. Be patient.

You don’t need to stop everything. But if you’re taking two or more anticholinergic drugs, or one strong one for over a year, it’s worth asking.

The Bigger Picture

The Lancet Healthy Longevity Commission named anticholinergic burden one of the top 10 modifiable risk factors for dementia-possibly contributing to 10-15% of cases. That’s like removing smoking or high blood pressure from the list of dementia causes.

Pharmaceutical companies are starting to respond. Johnson & Johnson stopped making long-acting oxybutynin in 2021. Pfizer pushed solifenacin, which is safer for the brain. The FDA now requires updated warning labels on all anticholinergic drugs. And the National Institute on Aging is funding a $14.7 million study to see if reducing these drugs can actually delay dementia.

But until that research is complete, the best tool we have is awareness. The brain changes caused by these drugs aren’t inevitable. They’re reversible. And they’re preventable.

When to Get Help

If you notice any of these signs in an older adult:

• Sudden confusion or disorientation
• Forgetting recent conversations or appointments
• Difficulty following instructions
• Slowed thinking or speech
• Increased falls or clumsiness

-ask: “Could this be from a medication?” Bring the list. Ask for an ACB score. Don’t assume it’s just aging.

The truth is, many of the cognitive changes we blame on getting older are actually caused by pills we never questioned. And that’s something we can fix.