Published: May 15, 2026 · Last updated: May 15, 2026
- A 2015 JAMA Internal Medicine study found that cumulative anticholinergic drug use over three years was associated with a 54% higher dementia risk in adults 65 and older (Harvard Health, 2024)
- Common anticholinergic drugs include Benadryl (diphenhydramine), Tylenol PM, oxybutynin for overactive bladder, doxepin for sleep, and tricyclic antidepressants (Harvard Health, 2024)
- Safer alternatives exist for most anticholinergic uses; the FDA Beers Criteria flags this drug class as inappropriate for adults over 65 except in specific circumstances (Harvard Health, 2024)
If you take Benadryl to sleep, Tylenol PM for headaches, or an overactive bladder medication, you are taking an anticholinergic. The class includes some of the most widely used over-the-counter products in America, and the evidence linking long-term use to dementia is now strong enough that the FDA, Harvard Medical School, and major geriatric societies all advise caution in adults over 65.
This is not a panic article. It is a list of practical swaps that protect your brain without sacrificing the symptoms you are actually trying to treat.
What Anticholinergic Drugs Do
Anticholinergic drugs block acetylcholine, a neurotransmitter the brain uses for learning, memory, and muscle control. In the body, acetylcholine also drives bladder contractions, gut motility, and many other involuntary functions. Anticholinergics were originally developed to block these peripheral effects for conditions like overactive bladder, allergies, and motion sickness. The brain effects were considered side effects.
Two decades of research now suggest those brain effects are not minor. Each anticholinergic dose temporarily reduces acetylcholine signaling in the brain. Chronic use, particularly in adults whose acetylcholine systems are already declining with age, appears to cause measurable cognitive damage that may not fully reverse (Harvard Health, 2024).
The 2015 JAMA Study That Shifted the Conversation
Researchers at the University of Washington tracked nearly 3,500 adults over 65 for an average of 7 years. They used pharmacy records to measure cumulative anticholinergic drug exposure over the prior 10 years. By study end, 797 participants had developed dementia.
The dose-response pattern was clear. Taking an anticholinergic at the equivalent of three years or more was associated with a 54% higher dementia risk compared to those with three months or less of exposure. The relationship persisted after adjusting for age, sex, education, and other risk factors. Subsequent studies in larger cohorts have replicated the finding.
Drugs to Recognize (And the Safer Alternatives)
The most-used anticholinergic over-the-counter is diphenhydramine, the active ingredient in Benadryl, Tylenol PM, Advil PM, ZzzQuil, and Sominex. The safer alternatives depend on what you are treating. For allergies, second-generation antihistamines (loratadine, cetirizine, fexofenadine) are nearly as effective without the brain effects. For occasional sleep, magnesium glycinate, melatonin, or cognitive behavioral therapy for insomnia (CBT-I) have far better risk profiles.
Other common offenders include oxybutynin and tolterodine for overactive bladder (alternatives: mirabegron, pelvic floor therapy, or beta-3 agonists), doxepin and amitriptyline (tricyclic antidepressants now largely replaced by SSRIs except for chronic pain), dimenhydrinate for motion sickness (alternative: meclizine, slightly less anticholinergic), and certain Parkinson's drugs that have no easy substitute but are usually prescribed by specialists who know the trade-off (Harvard Health, 2024).
The Cumulative Burden Concept
Geriatricians measure something called the Anticholinergic Cognitive Burden score, which sums up the anticholinergic activity of every medication a patient takes. A common scenario: an older adult takes Benadryl for sleep (score 3), oxybutynin for bladder (score 3), and amitriptyline for nerve pain (score 3) for a cumulative score of 9. That patient's dementia risk over 5 years is meaningfully higher than someone with a score of zero, even if no single drug seems alarming.
This is why a brown bag medication review with a pharmacist is one of the highest-yield preventive interventions for adults over 65. The pharmacist can calculate the total anticholinergic burden and recommend specific swaps that reduce the score without compromising symptom control.
What the Research Does Not Settle
Causation is not fully established. The studies are observational, which means they show association but cannot prove that anticholinergics cause dementia rather than tracking some other underlying factor. Randomized trials of dementia prevention through anticholinergic avoidance would take 10 to 20 years and have not been done. The current consensus is that the association is strong enough, plausible enough, and the alternatives are good enough that switching is the prudent recommendation, even if final proof is years away (Harvard Health, 2024).
If you have been taking a long-term anticholinergic, that does not mean dementia is inevitable. Stopping the drug appears to reduce risk going forward, though the brain may not fully recover whatever cognitive ground was lost.
To your health,
Ageless Coach
Age Strong. Live Long.
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