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

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

A growing body of research has focused on repurposing existing medications for Alzheimer's disease prevention. Among the candidates evaluated, three have 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 has emerged as a 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 landmark natural experiment published in Nature in 2023 by Eyting and colleagues compared dementia rates in Welsh populations where shingles vaccination eligibility was determined by birth date, effectively creating a natural controlled comparison. The results showed significantly lower dementia incidence among vaccinated cohorts, providing some of the strongest causal evidence to date for a protective effect.

Sildenafil, a phosphodiesterase-5 inhibitor, was identified as a promising Alzheimer's candidate in a 2021 study published in Nature Aging by Fang and colleagues, which used computational approaches and insurance claims data to find that sildenafil use was associated with a substantially reduced risk of Alzheimer's disease. The drug has also 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.

The Eyting et al. natural experiment published in Nature provided some of the most compelling causal evidence by exploiting a policy change in Wales that created clearly defined vaccinated and unvaccinated groups based on birth date alone. The study found that eligibility for the shingles vaccine was associated with a meaningful reduction in dementia diagnoses over a seven-year follow-up period. Subsequent observational studies have further supported this association, with some research suggesting that the newer recombinant vaccine (Shingrix) may offer even greater neuroprotective benefits compared to the older live vaccine (Zostavax), possibly due to its stronger immune response.

What Are the Implications for Alzheimer's Prevention?

The implications of these findings are substantial. Alzheimer's disease affects approximately 55 million people worldwide according to the World Health Organization, and current disease-modifying therapies — such as lecanemab (Leqembi) and donanemab (Kisunla) — are expensive (approximately $26,500 per year for lecanemab), 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.

Experts have 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 have expressed interest in conducting 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. 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). The vaccine is primarily recommended for shingles prevention, where its efficacy is well established at over 90% in clinical trials, and any cognitive benefits would be an additional advantage.