Study Raises Alarm: Common Antiviral May Speed Up Cognitive Decline

A well-known antiviral drug commonly prescribed for herpes infections may be doing more harm than good in people with early Alzheimer’s disease, according to a new clinical trial. Rather than slowing cognitive decline, the medication valacyclovir was linked to faster deterioration in thinking and memory compared with a placebo over an 18-month study period. These surprising findings challenge hopes that antiviral therapy could offer a new way to treat Alzheimer’s symptoms tied to viral infection hypotheses.

The randomized, double-blind trial, published in JAMA, enrolled 120 adults with early symptomatic Alzheimer’s disease or mild cognitive impairment who also showed evidence of herpes simplex virus (HSV) exposure. Participants were assigned either high-dose valacyclovir or a placebo and followed for 78 weeks.

Instead of offering benefits, those taking valacyclovir experienced a significantly greater increase in cognitive impairment scores nearly 11 points on a standard Alzheimer’s assessment scale than the placebo group, whose scores rose by about 7 points.

Why scientists hoped antivirals might help Alzheimer’s

Some research has suggested that viral infections particularly herpes simplex virus type 1 (HSV-1) may contribute to Alzheimer’s disease by interacting with brain proteins tied to plaques and tangles. Autopsy studies have found HSV-1 DNA in Alzheimer’s-related plaques, leading some scientists to theorize that antiviral drugs might reduce viral triggers of neurodegeneration.

Cell culture and animal experiments have shown that antiviral medications can reduce viral particles and lower harmful protein accumulations linked to Alzheimer’s pathology, which fueled hopes that repurposed herpes drugs could offer therapeutic benefit.

Valacyclovir, a widely used oral antiviral medication, was chosen for its ability to target HSV and its established safety profile in treating conditions like cold sores and shingles. Researchers hoped that, if viruses played a meaningful role in cognitive decline, suppressing them might slow disease progression.

What the clinical trial actually found

The trial’s primary measure was cognitive function over the 78-week period, assessed using the Alzheimer’s Disease Assessment Scale-Cognitive Subscale. Participants in the valacyclovir group saw a greater worsening of scores, suggesting faster cognitive decline compared with those on the placebo.

Secondary measures, including daily functioning and brain imaging for hallmark Alzheimer’s proteins (amyloid and tau), showed no significant differences between groups. That means while cognition worsened faster with valacyclovir, there was no clear change in structural brain markers tied to Alzheimer’s pathology

Researchers concluded that valacyclovir did not provide cognitive benefit and may even worsen outcomes for individuals with early symptomatic Alzheimer’s disease who are HSV-seropositive. They do not recommend its use for this purpose, although the reasons for the observed effect remain unclear.

What this means for Alzheimer’s treatment research

The study’s unexpected result highlights the gap between promising lab evidence and real-world clinical outcomes. Even though antivirals reduced harmful proteins in cell and animal models, this didn’t translate into slower decline, and may have had the opposite effect in humans.

Experts stress that while this trial does not support using valacyclovir to treat Alzheimer’s symptoms, it does not completely rule out a viral link to neurodegeneration. It may be that antiviral strategies need to target much earlier stages of the disease or be paired with other therapies. Ongoing trials are exploring related questions, including in people with mild cognitive impairment.

For now, the verdict is clear: valacyclovir doesn’t help, and may even harm cognitive outcomes for people with early Alzheimer’s and past HSV infection. The findings remind researchers and families alike that even familiar drugs can have unexpected effects, and rigorous testing remains essential in the long search for effective Alzheimer’s treatments.