Benadryl Side Effects on Brain Health and Dementia Risk First-generation antihistamines like diphenhydramine (Benadryl) block histamine but also strongly block acetylcholine, a neurotransmitter essential for attention and memory. That anticholinergic effect explains many of the cognitive risks. 🧠 Memory problems and slower thinking Diphenhydramine crosses the blood–brain barrier and impairs attention, working memory, and reaction time. Controlled studies show worse vigilance and cognitive perfo