TL;DR
A growing body of evidence links long-term use of diphenhydramine to cognitive decline and dementia risk — and the drug is still sold without a warning.
MSM Perspective
CNN Health ran the latest study as a wellness segment with 'should you worry?' framing instead of asking why the FDA hasn't acted on five years of converging data.
X Perspective
Medical X has been sounding the anticholinergic alarm for years — the peer-reviewed evidence caught up, and the FDA still hasn't updated the labeling.
A study published Friday in JAMA Neurology by researchers at the Indiana University School of Medicine found that adults who took diphenhydramine — the active ingredient in Benadryl, ZzzQuil, and numerous over-the-counter sleep aids — for three or more years showed a 54 percent increased risk of developing dementia compared to non-users. The study followed 3,400 participants over ten years, controlling for age, education, cardiovascular risk, and baseline cognitive function. [1]
This is the fifth major study in three years to link long-term anticholinergic use to cognitive decline. A 2023 University of Washington study found a 63 percent increased risk. A 2024 Nottingham meta-analysis across 350,000 patients found a dose-response relationship — the more you take, the higher the risk. A 2024 Harvard study found measurable changes in brain structure via MRI in chronic users. The Indiana study adds the longest follow-up period and the most granular dosage tracking. [1] [2]
Diphenhydramine blocks acetylcholine, a neurotransmitter essential for memory formation. The mechanism by which anticholinergics might contribute to cognitive decline is biologically plausible and well understood pharmacologically. The FDA's current labeling for diphenhydramine includes warnings about drowsiness, dizziness, and interactions with alcohol. It does not mention cognitive decline. It does not mention dementia risk. [2]
On medical X, the response was not surprise but frustration. Physicians specializing in geriatrics and neurology have been recommending against long-term anticholinergic use for years, citing the Beers Criteria — a list of medications the American Geriatrics Society considers potentially inappropriate for older adults. Diphenhydramine has been on the Beers list since 2012. The clinical community moved. The labeling did not. The over-the-counter market did not. Americans purchased an estimated $680 million worth of diphenhydramine products in 2025. [1]
The question is not whether the evidence is sufficient. Five studies in three years is sufficient. The question is why the FDA has not acted on it.
-- NORA WHITFIELD, Chicago
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