Overview

• Participants receiving high-dose valacyclovir experienced greater cognitive decline on the ADAS-Cog11 than those on placebo, with a 3.91-point difference at 78 weeks (95% CI 1.03–6.8).
• No significant differences emerged in functional assessments, MoCA scores or imaging biomarkers including amyloid PET, tau PET, cortical thickness and hippocampal volume.
• The double-blind trial enrolled 120 adults with mild Alzheimer’s dementia or mild cognitive impairment who tested seropositive for HSV-1 or HSV-2 and met positive Alzheimer’s biomarker criteria.
• Valacyclovir was confirmed to penetrate the central nervous system and was well tolerated, but it did not slow disease progression.
• Investigators recommend against using antivirals for early Alzheimer’s treatment and call for prospective prevention trials to explore long-term antiviral strategies following herpes infection.