Anticholinergic Burden in Older Adults: How Common Medications Affect Memory and Thinking

Many older adults take medications every day to manage pain, allergies, overactive bladder, or depression. But what if some of those everyday pills are quietly harming their memory and thinking? That’s the reality of anticholinergic burden-a hidden risk that’s quietly affecting millions of seniors.

What Exactly Is Anticholinergic Burden?

Anticholinergic burden is the total effect of all the medications a person takes that block acetylcholine, a brain chemical critical for memory, attention, and learning. It’s not about one drug-it’s about the cumulative impact of multiple drugs, even if each one seems harmless on its own.

Think of it like filling a bucket with water. One cup of water won’t spill over. But keep adding cups-diphenhydramine from allergy pills, oxybutynin for bladder control, amitriptyline for sleep or pain-and eventually, the bucket overflows. In the brain, that overflow shows up as confusion, forgetfulness, and slower thinking.

The most widely used tool to measure this is the Anticholinergic Cognitive Burden (ACB) scale. It rates each drug from Level 1 (mild) to Level 3 (strong). A person taking two Level 2 drugs and one Level 3 drug has an ACB score of 7. Research shows that scores of 3 or higher are linked to measurable cognitive decline.

Which Medications Carry the Highest Risk?

Not all anticholinergic drugs are the same. Some are obvious-like Benadryl or older antidepressants. Others are less known, even to doctors.

• First-generation antihistamines: Diphenhydramine (Benadryl), chlorpheniramine. Used for allergies, colds, or sleep. These cross the blood-brain barrier easily and are among the most common culprits.
• Overactive bladder drugs: Oxybutynin, tolterodine, solifenacin. Oxybutynin is a Level 3 drug-strong anticholinergic effect. Many seniors take it for years without knowing the brain risks.
• Tricyclic antidepressants: Amitriptyline, nortriptyline. Still prescribed for nerve pain or depression, even though safer SSRIs exist.
• Anti-Parkinson’s and antipsychotics: Benztropine, clozapine. Used less often, but still carry high ACB scores.

In 2022, about 10% of adults over 65 in the U.S. were taking medications with strong anticholinergic effects. That’s over 5 million people. And nearly 80% of those prescriptions were for conditions where safer, non-anticholinergic alternatives exist.

How Do These Drugs Actually Hurt the Brain?

Acetylcholine isn’t just a chemical-it’s the brain’s main signal for memory formation and focus. The M1 muscarinic receptors, where anticholinergics block this signal, are packed in the hippocampus and frontal cortex-areas responsible for remembering names, planning tasks, and staying focused.

Brain scans tell a clear story. A 2016 study in JAMA Neurology found that older adults taking medium-to-high ACB drugs had 4% less glucose metabolism in the temporal lobe-the same region that shrinks in early Alzheimer’s. Even people without dementia showed this pattern.

MRI studies from the Indiana Memory and Aging Study showed that long-term users of anticholinergics had brain shrinkage rates 0.24% faster per year than non-users. That might sound small, but over five years, it adds up to noticeable structural changes.

And it’s not just structure-it’s function. The ASPREE study, which followed nearly 20,000 seniors over nearly five years, found that each 1-point increase in ACB score led to:

• 0.15-point greater decline per year in executive function (planning, problem-solving)
• 0.08-point greater decline per year in verbal memory (remembering lists or stories)

Processing speed was less affected, which tells us these drugs don’t slow down the whole brain-they target the parts that matter most for daily independence.

Long-Term Use = Higher Dementia Risk

The biggest fear? That these drugs might not just cause temporary confusion-but actually increase the chance of developing dementia.

A landmark 2015 study in JAMA Internal Medicine tracked over 3,400 older adults for more than a decade. Those who took strong anticholinergic drugs for three years or more had a 54% higher risk of dementia than those who used them for less than three months. Even after adjusting for other health conditions, the link held strong.

This isn’t just correlation. The dose-response pattern is clear: more drugs, longer use, higher risk. And it’s not reversible overnight. The brain doesn’t bounce back in a week. The DICE trial showed that after 12 weeks of stopping anticholinergics, seniors saw small but meaningful improvements in cognitive test scores. But full recovery can take months-or may never be complete if damage has been long-standing.

Real People, Real Consequences

Behind the statistics are real lives.

One caregiver on AgingCare.com wrote: “My mom was constantly confused, forgetting meals, mixing up names. We thought it was early dementia. Then her pharmacist flagged oxybutynin as a strong anticholinergic. We stopped it. Within two weeks, she was back to herself. Her doctor had no idea it was the cause.”

The FDA recorded over 1,200 cognitive-related adverse events in seniors from 2018 to 2022. Confusion was the most common. Memory loss came second. Delirium-sudden, severe mental confusion-was third.

And here’s the kicker: 63% of older adults surveyed by the National Council on Aging said they were never told about the cognitive risks when these drugs were prescribed. Most assumed the doctor had checked for safety. They didn’t know they were being given a silent threat.

What Can Be Done?

The good news? This is one of the few dementia risk factors we can actually change.

The American Geriatrics Society’s 2023 Beers Criteria says: avoid strong anticholinergics in older adults. Period. And there are alternatives.

• For allergies: Use non-sedating antihistamines like loratadine or cetirizine. They don’t cross into the brain.
• For overactive bladder: Mirabegron (Myrbetriq) works differently-no anticholinergic effect. Pelvic floor therapy is also effective.
• For depression: SSRIs like sertraline or escitalopram have little to no anticholinergic activity.
• For sleep: Melatonin or cognitive behavioral therapy for insomnia (CBT-I) are safer than diphenhydramine.

The challenge? Many doctors don’t have time. A 2021 survey found that primary care physicians need an average of 23 minutes to review a senior’s full medication list for anticholinergic risk. But most appointments are 15 minutes or less.

Tools like the ACB Calculator app, launched by the American Geriatrics Society in 2024, help. You plug in a list of medications, and it gives you the total ACB score in seconds. Pharmacists are also stepping up-many now flag high-risk combinations during refill reviews.

What Should Seniors and Families Do?

You don’t need to stop meds cold turkey. But you do need to ask questions.

• Ask your doctor or pharmacist: “Is this medication anticholinergic? What’s the risk to my memory?”
• Ask: “Is there a non-anticholinergic alternative?”
• If you’ve been on a drug like oxybutynin or diphenhydramine for more than a year, ask about tapering it off.
• Keep a full list of all medications-including OTC and supplements-and bring it to every appointment.
• If you notice sudden confusion, forgetfulness, or trouble focusing after starting a new med, talk to your doctor immediately.

It’s not about fear. It’s about awareness. Many of these drugs were prescribed decades ago, before we understood their long-term brain effects. Now we know. And knowing changes everything.

What’s Next?

The National Institute on Aging is funding a major study called CHIME, launching in 2024, to test whether actively reducing anticholinergic burden can delay or prevent cognitive decline in 3,500 seniors. Results are expected by 2027.

Meanwhile, pharmaceutical companies are responding. Johnson & Johnson stopped making long-acting oxybutynin in 2021. Pfizer’s solifenacin, with less brain penetration, now holds over 20% of the bladder drug market.

The European Medicines Agency and FDA have both updated warnings on anticholinergic labels. But warnings mean little if patients don’t understand them.

The real change will come when doctors, pharmacists, and families start asking the same question: “Could this pill be hurting my brain?”