Vaccines hold tantalizing promise in the fight against dementia

Over the past two centuries, vaccines have been critical for preventing infectious diseases. The World Health Organization estimates that vaccination prevents between 3 million and 5 million deaths annually from diseases like diphtheria, tetanus, influenza, measles and, more recently, COVID-19.

While there has long been broad scientific consensus that vaccines prevent or mitigate the spread of infections, there is new research suggesting that the therapeutic impact might go beyond the benefit of preventing infectious diseases.

An April 2025 study published in the prominent journal Nature found tantalizing evidence that the herpes zoster – or shingles – vaccine could lower the risk of dementia in the general population by as much as 20%.

We are a team of physician scientists with expertise in the clinical and basic science of neurodegenerative disorders and dementia.

We believe that this study potentially opens the door to other breakthroughs in understanding and treating dementia and other degenerative disorders of the brain.

A role for vaccines in reducing dementia risk?

One of the major challenges researchers face when trying to study the effects of vaccines is finding an unvaccinated “control group” for comparison – a group that is similar to the vaccine group in all respects, save for the fact that they haven’t received the active vaccine. That’s because it’s unethical to assign some patients to the control group and deprive them of vaccine protection against a disease such as shingles.

The Nature study took advantage of a policy change in Wales that went into effect in 2013, stating that people born on or after September 2, 1933, were eligible for the herpes zoster vaccination for at least a year, while those born before that cutoff date were not. The vaccine was administered to prevent shingles, a painful condition caused by the same virus that causes chickenpox, which can lie dormant in the body and be reactivated later in life.

The researchers used the policy change as a natural laboratory of sorts to study the effect of shingles vaccination on long-term health outcomes. In a statistically sophisticated analysis of health records, the team found that the vaccine reduced the probability of getting dementia by one-fifth over a seven-year period. This means that people who received the shingles vaccine were less likely to develop clinical dementia over the seven-year follow-up period, and women benefited more than men.

The study design allowed researchers to compare two groups without actively depriving any one group of access to vaccination. The two groups were also of comparable age and had similar medical comorbidities – meaning similar rates of other medical conditions such as diabetes or high blood pressure.

Results from this and other related studies raise the possibility that vaccines may have a broader role in experimental therapeutics outside the realm of infectious diseases.

These studies also raise provocative questions about how vaccines work and how our immune system can potentially prevent dementia.

How vaccines might be protective

One scientific explanation for the reduction of dementia by the herpes zoster vaccine could be the direct protection against the shingles virus, which may play a role in exacerbating dementia.

However, there is also the possibility that the vaccine may have conferred protection by activating the immune system and providing “trained immunity,” in which the immune system is strengthened by repeated exposure to vaccines or viruses.

The study did not differentiate between different types of dementia, such as dementia due to Alzheimer’s disease or dementia due to stroke. Additionally, researchers cannot draw any definitive conclusions about possible mechanisms for how the vaccines could be protective from an analysis of health records alone.

The next step would be a prospective, randomized, double-blind, placebo-controlled study – the “gold standard” for clinical trials in medicine – to directly examine how the herpes zoster vaccine compares with a placebo in their ability to reduce the risk of dementia over time. Such studies are necessary before any vaccines, as well as other potential therapies, can be recommended for routine clinical use in the prevention of dementia.

The challenges of untangling dementia

Dementia is a major noncommunicable disease that is a leading cause of death around the world.

A January 2025 study provided updated figures on lifetime dementia risk across different subsets of the U.S. population. The researchers estimate that the lifetime risk of dementia after age 55 is 42% – more than double earlier estimates. The dementia risk was 4% by age 75, and 20% by age 85, with the majority of risk occurring after 85. The researchers projected that the number of new cases of dementia in the U.S. would double over the next four decades from approximately 514,000 cases in 2020 to 1 million in 2060.

Once considered a disease largely confined to the developed world, the deleterious effects of dementia are now apparent throughout the globe, as life expectancy increases in many formerly developing countries. While there are different forms of dementia with varying clinical manifestations and underlying neurobiology, Alzheimer’s disease is the most common.

Prospective studies that specifically test how giving a vaccine changes the risk for future dementia may benefit from studying patient populations with specific types of dementia because each version of dementia might require distinct treatments.

Unfortunately, for the past two to three decades, the amyloid hypothesis of Alzheimer’s disease – which posits that accumulation of a protein called amyloid in the brain contributes to the disorder – dominated the scientific conversation. As a result, most of the efforts in the experimental therapeutics of Alzheimer’s disease have focused on drugs that lower the levels of amyloid in the brain.

However, results to date have been modest and disappointing. The two recently approved amyloid-lowering therapies have only a minimal impact on slowing the decline, are expensive and have potentially serious side effects. And no drug currently approved by the Food and Drug Administration for clinical use reverses the cognitive decline.

Studies based on health records suggest that past exposure to viruses increase the risk of dementia, while routine vaccines, including those against tetanus, diphtheria, pertussis, pneumonia, shingles and others, reduce the risk.

Innovation and an open mind

There is sometimes a tendency among scientists to cling to older, familiar models of disease and a reluctance to move in more unconventional directions.

Yet the process of doing science has a way of teaching researchers like us humility, opening our minds to new information, learning from our mistakes and going where that data takes us in our quest for effective, lifesaving therapies.

Vaccines may be one of those paths less traveled. It is an exciting possibility that may open the door to other breakthroughs in understanding and treating degenerative disorders of the brain.

Jalees Rehman receives funding from NIH.

Anand Kumar does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.