Popular allergy and sleep aids like Benadryl may quietly cloud memory over years

The pink tablets sold as Benadryl and the sleep aids marketed under names like Tylenol PM and ZzzQuil share an active ingredient, diphenhydramine, that has been on pharmacy shelves for generations. It is effective against allergy symptoms and reliably makes people drowsy, which is why it appears in so many nighttime remedies. Over the past decade, however, a body of research has raised a more troubling question about the class of drugs to which diphenhydramine belongs. Long-term, heavy use of these medicines, known as anticholinergics, has been associated in several large studies with a higher risk of dementia, and the effect may build gradually over years of routine use.

What anticholinergic drugs actually do

Anticholinergics work by blocking acetylcholine, a chemical messenger that nerve cells use to communicate. Acetylcholine helps control muscles, glands and, importantly, functions in the brain related to learning and memory. Diphenhydramine is a first-generation antihistamine, meaning it crosses easily into the brain, which is why it causes sedation. Many other common medicines have anticholinergic effects as well, including certain drugs for overactive bladder, depression, Parkinson’s disease and gastrointestinal problems. Because acetylcholine is central to memory and cognition, and because the brain’s supply of it tends to fall with age and with diseases like Alzheimer’s, researchers have long suspected that persistently blocking it could carry consequences for the aging brain.

The landmark study on cumulative use

The most influential evidence came from a study published in 2015 in JAMA Internal Medicine. Researchers followed 3,434 adults aged 65 and older, none of whom had dementia when the study began, and tracked their use of anticholinergic medicines over roughly a decade using pharmacy records. As the published findings reported, people with the highest cumulative exposure to strong anticholinergics had a substantially elevated risk of developing dementia compared with those who took none. The heaviest users faced a relative risk of dementia raised by roughly 54 percent, and a risk of Alzheimer’s disease specifically raised by about 63 percent. The exposure at the top of the range corresponded to taking a standard daily dose of a strong anticholinergic for three years or more.

What “cumulative” means for everyday medicines

A key nuance of the research is that it concerns total exposure built up over time, not a single occasional dose. The study measured how much of these drugs a person had taken across years, so the elevated risk was linked to sustained, long-term use rather than to taking a Benadryl now and then for an allergic reaction. Diphenhydramine was among the medicines identified as strong anticholinergics in this body of work, alongside certain tricyclic antidepressants and bladder-control drugs. Later research reinforced the pattern. A 2019 study in JAMA Internal Medicine using a large British primary-care database found that greater anticholinergic exposure, particularly from antidepressants, bladder medicines, antipsychotics and anti-epileptic drugs, was associated with increased dementia risk, adding weight to the earlier findings.

Association is not the same as proof

The studies establish a strong and repeated association, but they do not by themselves prove that anticholinergic drugs cause dementia. These are observational studies, which means researchers watched what happened to people taking the medicines rather than assigning treatments in a controlled trial. That design leaves room for other explanations. One important possibility is reverse causation: the earliest, undiagnosed stages of dementia can produce symptoms such as depression, sleep disturbance and bladder problems, the very conditions these drugs are prescribed to treat. In that scenario, heavy use of anticholinergics could partly be an early sign of brain changes rather than a cause of them. Scientists writing about the topic, including in Scientific American, have emphasized that the link is credible and worth acting on cautiously, while stopping short of declaring the case closed.

Why experts still urge caution

Despite that uncertainty, geriatric specialists have moved toward recommending that older adults limit long-term use of strong anticholinergics where safer alternatives exist. Diphenhydramine appears on lists of medicines that clinicians are advised to avoid in older patients, in part because of its anticholinergic burden and its tendency to cause confusion, falls and next-day grogginess even in the short term. For allergies, newer antihistamines such as loratadine and cetirizine cause far less sedation and have little anticholinergic effect on the brain. For occasional sleeplessness, sleep specialists generally favor behavioral approaches over nightly reliance on sedating antihistamines. The consistent message from the research is that these drugs are best used sparingly, especially by people who might otherwise take them night after night for months or years.

What the evidence adds up to

Taken together, the studies paint a picture worth taking seriously without inviting alarm. There is no evidence that a rare dose of a diphenhydramine product harms the brain, and these medicines remain useful tools for acute allergic reactions and short-term relief. What the research flags is the pattern of long-term, heavy use in older adults, which multiple large investigations have tied to a meaningfully higher risk of dementia. Because the potential harm accumulates quietly and the drugs are so easy to obtain, health authorities and researchers increasingly encourage patients and clinicians to review chronic anticholinergic use and to weigh lower-risk alternatives. The prudent takeaway from the science is not fear of an occasional tablet, but attention to how often, and for how long, these familiar remedies are being used.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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