JAMA

Valacyclovir fails to slow cognitive decline in early Alzheimer's

December 19, 2025

Valacyclovir didn’t significantly slow cognitive or functional decline compared with placebo in patients with early symptomatic Alzheimer's disease [AD] who were herpes simplex virus (HSV)-seropositive, according to the VALAD randomized trial (NCT03282916). In the 78-week phase 2 study, 120 participants were enrolled and 93 completed the trial. All had probable AD or mild cognitive impairment and HSV antibodies and were randomized to valacyclovir (up to 4 g daily) or placebo. Neither the primary outcome (Alzheimer's Disease Assessment Scale-Cognitive Subscale) nor secondary clinical measures showed significant between-group differences.

Clinical takeaway: Despite biological plausibility linking HSV to AD pathology, valacyclovir doesn’t appear to be an effective disease-modifying treatment for early AD in HSV-seropositive patients.

Source:

Devanand DP, et al. (2025, December 17). JAMA. Valacyclovir Treatment of Early Symptomatic Alzheimer Disease: The VALAD Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41405855/