Anticholinergic Drugs and Dementia Risk: What the Evidence Actually Says

What Anticholinergic Drugs Are

Anticholinergic medications block acetylcholine, a neurotransmitter that helps carry signals for memory, attention, muscle movement, and many other functions. The same mechanism that dries up secretions or calms an overactive bladder can dampen cognitive processes in the brain.

They come from many different medicine cabinets — over-the-counter sleep aids and allergy pills, prescription bladder medicines, older antidepressants, some antipsychotics, muscle relaxants, and treatments for Parkinson's disease. Adults over 65 often take more than one without realizing the load adds up.

The American Geriatrics Society's Beers Criteria for potentially inappropriate medications in older adults warns that "cumulative exposure to anticholinergic drugs is associated with an increased risk of falls, delirium, and dementia" (AGS 2023 Beers Criteria).

Key Facts at a Glance

• Gray and colleagues (2015) followed 3,434 adults aged 65+ for over seven years and found the highest cumulative anticholinergic exposure carried a hazard ratio of 1.54 for all-cause dementia and 1.63 for Alzheimer's disease (Gray et al., 2015).
• Coupland and colleagues (2019) analyzed nearly 285,000 people in UK primary care and reported an adjusted odds ratio of 1.49 in the highest exposure group (Coupland et al., 2019).
• Not every anticholinergic looks equally risky. A 2024 BMJ Medicine study found dose-related dementia associations for oxybutynin, solifenacin, and tolterodine but not for several newer bladder alternatives (Iyen et al., 2024).
• A 2025 systematic umbrella review in Molecular Psychiatry pooled meta-analyses and found moderate-certainty evidence that anticholinergic drugs increase dementia risk (Belessiotis-Richards et al., 2025).
• These are observational studies. They cannot prove that stopping an anticholinergic will lower an individual's dementia risk, and confounding is always possible.
• Geriatric guidelines still emphasize minimizing strong anticholinergic use in older adults when a safer option exists.

What the Research Actually Found

Two large studies, one consistent signal

The clearest signal comes from two rigorous studies. In 2015, Gray and colleagues published a prospective cohort in JAMA Internal Medicine following older adults in Seattle. Participants with the greatest cumulative exposure — roughly three or more years of daily strong-anticholinergic use — had a 54 percent higher hazard of any dementia and a 63 percent higher hazard of Alzheimer's disease compared with no use (Gray et al., 2015).

In 2019, Coupland and colleagues used a much larger UK primary-care database, comparing 58,769 people with dementia to 225,574 matched controls. Adjusted odds ratios rose stepwise with exposure and reached 1.49 in the highest group (Coupland et al., 2019). Risk was strongest for anticholinergic antidepressants, antipsychotics, antiparkinson drugs, bladder antimuscarinics, and antiepileptics — and less consistent for antihistamines.

Overactive bladder: a closer look

Bladder medicines are especially common in older adults. A 2024 study in BMJ Medicine matched 170,742 dementia cases with 804,385 controls and analyzed each drug separately. Dose-response increases in dementia risk appeared for oxybutynin, solifenacin, and tolterodine, while several newer bladder anticholinergics — darifenacin, fesoterodine, and trospium among them — did not show a significant increase (Iyen et al., 2024).

The umbrella-review view

A 2025 systematic umbrella review in Molecular Psychiatry pooled existing meta-analyses across drug classes. Its authors concluded there is moderate-certainty evidence that anticholinergic drugs increase dementia risk, and recommended assessment of anticholinergic burden during routine clinical visits (Belessiotis-Richards et al., 2025).

What the numbers do not tell you

The Alzheimer's Association reminds readers that "there is currently no strong evidence that any medications directly increase the risk of Alzheimer's or other dementia" — meaning links have not been confirmed by large clinical trials (Alzheimer's Association, 2024). Association is not causation. The signal is worth respecting; it does not prove any specific prescription caused any specific person's dementia.

Which Drug Classes Carry the Strongest Signal

Not every anticholinergic looks the same in the evidence. The classes with the most consistent association with dementia risk include:

• Tricyclic antidepressants (for example, amitriptyline and older agents used off-label for sleep and chronic pain).
• Certain antipsychotics used for behavioral symptoms.
• Antiparkinson anticholinergics (used less commonly today).
• Bladder antimuscarinics — with oxybutynin, solifenacin, and tolterodine drawing the most concern in the newest data.
• Some antiepileptic drugs.

First-generation antihistamines and some antispasmodics show weaker signals, though they remain flagged as inappropriate for older adults on the Beers Criteria because of falls, confusion, and delirium risk even setting dementia aside.

For a wider view across drug classes that affect cognition — including a different mechanism where the evidence tilts the other way — see our pillar guide to medications and cognition and our post on how statins can affect memory.

When to Talk to Your Prescriber

Some situations make a medication review particularly worthwhile:

• You are 65 or older and take one or more strong anticholinergic drugs long term.
• You have noticed a change in memory or attention that started after a new prescription, dose increase, or added OTC medication.
• You take drugs from several prescribers and no one has recently reviewed the full list together.
• You have a family history of dementia and would like to lower any avoidable exposures.
• You have side effects like dry mouth, constipation, blurred vision, or urinary retention, which suggest anticholinergic burden may be adding up.

If the symptoms feel more like transient fog than steady memory decline, our guide to brain fog versus cognitive decline walks through how to tell them apart. Other treatable conditions can look similar; our overview of reversible causes of memory loss covers the ones worth ruling out first.

What to Do (and Not Do)

The single most important rule: do not stop an anticholinergic on your own. Some of these medications treat serious conditions and abrupt discontinuation can cause rebound symptoms or withdrawal. A few practical steps make a conversation with your prescriber more productive:

1. Bring the full list. Every prescription, every OTC medication, and every supplement, with doses.
2. Ask specifically about anticholinergic burden. Not every clinician will bring it up. It is a fair, specific question to ask about your list.
3. Ask about alternatives. Many strong anticholinergics have safer substitutes, and non-drug options exist for conditions like overactive bladder and insomnia.
4. If a change is made, plan a follow-up to check whether the cognitive symptoms you noticed shift too.

Cognitive testing does not diagnose a medication side effect, but a short baseline — before a change, after a change, and periodically over time — gives you and your prescriber a personal reference point instead of a general sense of feeling different.

Taking the Next Step

For the wider picture across drug classes most often linked to cognitive change, start with our overview of medications that can cause memory loss.

If you'd like a structured, repeatable way to track attention, memory, and processing speed before or after a medication review, explore how Orena's at-home cognitive test works.