Shingles Vaccine May Protect Against Alzheimer's: New Study Identifies Three Repurposed Drugs

What Did the New Alzheimer's Drug Repurposing Study Find?

The study, published in February 2026, brought together leading researchers in neurology, pharmacology, and geriatrics to systematically evaluate existing medications for potential benefits against Alzheimer's disease. Among the 80 drugs reviewed, three stood out based on the strength of observational evidence, biological plausibility, and safety profiles: the recombinant zoster vaccine (Shingrix), sildenafil (marketed as Viagra for erectile dysfunction), and riluzole (currently approved for amyotrophic lateral sclerosis).

The shingles vaccine emerged as the frontrunner for several reasons. It requires only two doses, has an established safety record spanning millions of administered doses worldwide, and multiple large-scale observational studies have consistently shown an association between shingles vaccination and reduced dementia risk. A study published in Nature Communications found that two doses of recombinant zoster vaccine were associated with a 51% reduction in the risk of dementia in adults aged 65 years and older — a remarkably large effect size for a non-pharmacological intervention targeting neurodegeneration.

Sildenafil, a phosphodiesterase-5 inhibitor, has shown neuroprotective properties in preclinical studies, including improvements in cerebral blood flow and reduction of tau phosphorylation. Riluzole, which modulates glutamate signaling, has demonstrated potential to protect against excitotoxic neuronal damage, a process implicated in Alzheimer's pathology. However, both drugs would require more extensive clinical testing before they could be recommended for dementia prevention.

How Could the Shingles Vaccine Protect Against Dementia?

The biological mechanism linking shingles vaccination to dementia protection is an active area of investigation, but several hypotheses have emerged. The varicella-zoster virus (VZV), which causes both chickenpox and shingles, establishes lifelong latency in sensory nerve ganglia after initial infection. When the virus reactivates — causing shingles — it triggers significant neuroinflammation that may contribute to or accelerate neurodegenerative processes, including the accumulation of amyloid-beta plaques and tau tangles characteristic of Alzheimer's disease.

By preventing shingles reactivation, the vaccine may reduce episodes of neuroinflammation that could otherwise contribute to cognitive decline. Additionally, the immune system changes that occur with aging — collectively termed immunosenescence — are known to play a role in Alzheimer's pathology. The recombinant shingles vaccine contains an adjuvant (AS01B) that produces a robust immune response, and researchers theorize that this broad immune activation may have beneficial effects on the brain's immune surveillance and waste clearance mechanisms, including the glymphatic system responsible for clearing amyloid-beta during sleep.

A landmark natural experiment published in Nature in 2025 compared dementia rates in populations where shingles vaccination was introduced at different times, effectively creating a controlled comparison. The results showed significantly lower dementia incidence among vaccinated cohorts, providing some of the strongest causal evidence to date. Researchers at Stanford also found that among people already living with dementia, the shingles vaccine appeared to slow disease progression, suggesting benefits even after neurodegeneration has begun.

What Are the Implications for Alzheimer's Prevention?

The implications of these findings are substantial. Alzheimer's disease affects approximately 57 million people worldwide, and current disease-modifying therapies — such as lecanemab (Leqembi) and donanemab (Kisunla) — are expensive (approximately $26,500 per year), require intravenous infusion, and carry significant risks including amyloid-related imaging abnormalities (ARIA). A vaccine that is already approved, widely available, and covered by most insurance plans could represent a paradigm shift in dementia prevention.

The expert panel has called for randomized controlled trials specifically designed to test the shingles vaccine's effect on cognitive outcomes. Such trials would need to enroll large numbers of older adults, include comprehensive neuropsychological testing and biomarker assessments, and follow participants for several years to detect meaningful differences in dementia incidence. Several academic medical centers are reportedly in the planning stages for such trials, though funding and logistics remain significant challenges.

In the meantime, the existing evidence provides an additional reason for adults aged 50 and older to receive the recommended two-dose Shingrix vaccine series, which is already advised by the CDC for shingles prevention. The Centers for Disease Control and Prevention recommends Shingrix for all adults aged 50 years and older, regardless of whether they recall having had chickenpox or have previously received the older live zoster vaccine (Zostavax).