The Benadryl-Alzheimer’s-Dementia Connection: What You Need to Know

I truly believe Benadryl to be one of the wonder drugs no kit should be without.  As covered in previous blog posts, it treats anxiety, insomnia, hives, itching, bites, nausea, Parkinson’s, eczema, contact dermatitis, and so much more.  Few drugs have such a diverse array of applications. And because it is so useful, so inexpensive, and has such a long shelf-life, we stocked up. 

Then I learned that Benadryl use is contraindicated in those over the age of sixty.  All the herbal remedies I’d tried for insomnia just didn’t do the job.  How was I going to sleep at night?  I thought I solved the problem by moving to Unisom, doxylamine succinate.  I only took that when absolutely necessary because it left me hung over the next morning.  Even taking just ¼ of a tablet by 6:00 PM knocked me out.

And then Doc, my son-in-law in med school, informed me that Unisom was no better than Benadryl as far as avoiding Alzheimer’s was concerned.  Drat.  I thought others might have the same questions and concerns, so I decided that today was the day to do the research.  Might have something to do with not being able to sleep last night after having slept so well all summer.  (Four-five hours each day in the garden will do that.)

Diphenhydramine, the active ingredient in Benadryl, is a strong anti-cholinergic drug, meaning that it blocks acetylcholine, a neurotransmitter critical for memory, attention, and learning.  One long-term, observational study with 3434 participants aged 65 years and older who used anticholinergics frequently found that 23% developed dementia (79% of those cases were diagnosed as Alzheimer’s).[1]  It was also found that the greater the exposure—the more doses they took—the greater the subsequent risk of dementia.  And it didn’t matter whether the drugs had been used recently or years earlier.[2]  On the other hand, a 2019 study in the UK found no elevated risk in those who used antihistamines.[3]

Other research on older adults in Taiwan with allergic rhinitis found that the risk of dementia increased as the cumulative dose of antihistamines increased.[4] The association was observed with both first- and second-generation antihistamines, though it was greater with the first-generation drugs.[5]

And finally, the American Geriatrics Society (sad that some of us will soon be joining this cohort) also includes Benadryl in a significant list of pharmaceuticals to be avoided in treating older patients.[6]  In fact, I’d recommend checking the list included at this footnote when evaluating medications for older family members.  It was surprising to learn which medications may pose significant risks in older adults.  Most noteworthy are Benadryl, chlorpheniramine, dimenhydrinate (Dramamine), meclizine (Bonine), doxylamine (Unisom), nitrofurantoin, aspirin, warfarin, PPIs, and many NSAIDs.[7]

Please note that none of the articles stated that Benadryl or any of the other antihistamines and anticholinergics actually cause dementia.  There does appear to be a relationship and much further research is required.  Also, these studies involved frequent use of the medications.  Very occasional use, like for treating insect bites and stings, hives, etc., was not the focus of these studies. 

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[1] Gray SL, Anderson ML, Dublin S, et al. Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study. JAMA Intern Med. 2015;175(3):401–407. doi:10.1001/jamainternmed.2014.7663, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2091745/ (accessed 27 August 2026).

[2] Use of anticholinergic drugs linked to higher dementia risk, National Institute on Aging, 3 February 2015, https://www.nia.nih.gov/news/use-anticholinergic-drugs-linked-higher-dementia-risk (accessed 27 August 2026).

[3] Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. 2019;179(8):1084–1093. doi:10.1001/jamainternmed.2019.0677, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2736353 (accessed 27 August 2026).

[4] Su CH, Huang KH, Yang Y, Gau SY, Chung NJ, Wu PT, Tsai TH, Lee CY. Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis. J Allergy Clin Immunol Pract. 2024 Aug;12(8):2155-2165. doi: 10.1016/j.jaip.2024.05.027. Epub 2024 Jun 25. PMID: 38935035, https://pubmed.ncbi.nlm.nih.gov/38935035/ (accessed 27 August 2026).

[5] Su CH, Huang KH, Yang Y, Gau SY, Chung NJ, Wu PT, Tsai TH, Lee CY. Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis. J Allergy Clin Immunol Pract. 2024 Aug;12(8):2155-2165. doi: 10.1016/j.jaip.2024.05.027. Epub 2024 Jun 25. PMID: 38935035, https://pubmed.ncbi.nlm.nih.gov/38935035/ (accessed 27 August 2026).

[6] By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 Jul;71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4. PMID: 37139824; PMCID: PMC12478568, https://pmc.ncbi.nlm.nih.gov/articles/PMC12478568/ (accessed 27 August 2026).

[7] By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 Jul;71(7):2052-2081. doi: 10.1111/jgs.18372. Epub 2023 May 4. PMID: 37139824; PMCID: PMC12478568, https://pmc.ncbi.nlm.nih.gov/articles/PMC12478568/ (accessed 27 August 2026).