For Early Alzheimer’s, a Common Herpes Drug Fell Short

CATEGORY: BRAIN & MENTAL HEALTH

The antiviral didn’t work. Eighteen months of valacyclovir, a herpes drug taken safely by millions for cold sores and shingles, failed to slow early Alzheimer’s disease in a trial of 120 people. People taking it actually declined about 4 points more on a 70-point thinking test than people taking placebo.¹ For one of the most talked-about ideas in dementia research, that’s a hard result to hear.

Why Anyone Expected a Cold-Sore Drug to Fight Dementia

The idea wasn’t fringe. Herpes viruses have turned up in the brain tissue of people with Alzheimer’s, and the virus can nudge brain cells toward the disease’s hallmark changes in lab experiments. Large population studies added weight. In Wales, a natural experiment found that older adults who got a shingles vaccine were later diagnosed with dementia less often.² So the VALAD investigators made the obvious next move. They hypothesized that suppressing the herpes virus with a daily antiviral would slow decline in people who already had early Alzheimer’s and carried the virus.

Four Grams a Day, Measured Against a Lookalike Pill

The trial enrolled 120 adults with early symptomatic Alzheimer’s or mild cognitive impairment, confirmed by biomarkers, all of them carrying herpes simplex virus. Neither the patients nor their doctors knew who was swallowing the real drug; a random list decided. Treatment ran 78 weeks at 4 grams of valacyclovir a day. On the main measure, a cognitive test scored from 0 to 70 where higher means worse, the antiviral group worsened by 10.9 points and the placebo group by 6.9. The gap of 3.9 points favored placebo. Everyday functioning and brain scans of amyloid and tau, the disease’s two signature proteins, showed no meaningful differences.¹

What 120 People Can Settle, and What They Can’t

This was a modest-sized trial, and 27 people didn’t finish it. The signal that the drug made thinking worse rests on relatively few patients, so it deserves caution rather than alarm. The null result is the sturdier message: treating the virus didn’t slow the disease. Note what the trial doesn’t touch. It says nothing about shingles vaccination in healthy older adults, which is prevention, not treatment, and works through immunity rather than ongoing viral suppression. The viral theory of Alzheimer’s isn’t dead. But its most direct treatment test came back empty-handed, and the researchers concluded the drug shouldn’t be used for this purpose.

Key Takeaways

• Valacyclovir, tested because herpes viruses are linked to Alzheimer’s in population studies, didn’t slow decline over 78 weeks. The treated group scored about 4 points worse on cognition.
• Amyloid and tau on brain scans didn’t budge in either direction, undercutting the idea that viral suppression changes the disease’s biology.
• The result doesn’t bear on shingles vaccination, a different intervention that population data still favor. It bears on taking an antiviral to treat established Alzheimer’s, which this trial found unhelpful.

References

1. Devanand DP, Wisniewski T, Razlighi Q, et al. Valacyclovir Treatment of Early Symptomatic Alzheimer Disease: The VALAD Randomized Clinical Trial. JAMA. 2026;335(6):511–522. link
2. Eyting M, Xie M, Michalik F, Heß S, Chung S, Geldsetzer P. A natural experiment on the effect of herpes zoster vaccination on dementia. Nature. 2025;641(8062):438–446. link