The Sleeping Virus and the Ageing Brain

Article by Dr. Donald Greig

Shingles is one of those conditions that many people underestimate until they have seen it up close.

For some patients it is a painful, blistering rash that settles over a few weeks. For others, it can be far more disruptive: severe nerve pain, sleepless nights, secondary infection, eye involvement, scarring, or persistent pain that continues long after the rash has disappeared.

In recent months, shingles vaccination has attracted attention for another reason: the possibility that it may also be linked with a lower risk of dementia, including Alzheimer’s disease and other neurodegenerative conditions.

That is an intriguing possibility, but it needs careful wording. The shingles vaccine is proven to reduce the risk of shingles and post-herpetic neuralgia. The possible dementia benefit is not yet proven in the same way. The evidence so far is encouraging, but mostly observational rather than based on large randomised clinical trials specifically designed to test dementia prevention.

Still, the connection is scientifically interesting, and worth explaining.

What is shingles?

Shingles, also known as herpes zoster, is caused by the varicella-zoster virus.

This is the same virus that causes chickenpox. After a person has chickenpox, usually in childhood, the virus does not completely leave the body. Instead, it remains dormant in nerve tissue, often for decades.

Later in life, especially as the immune system becomes less vigilant with age, the virus can reactivate. When it does, it travels along a nerve and causes the painful rash we recognise as shingles.

The rash usually appears on one side of the body, often around the chest, abdomen, back or face. It may begin with tingling, burning, itching or pain before the blisters appear.

For some people, the most troublesome complication is post-herpetic neuralgia, a persistent nerve pain that can last for months or even years after the rash has healed. This can be extremely debilitating.

Shingles can also involve the eye, where it may threaten vision, and in some cases it can lead to neurological complications.

Why shingles becomes more common with age

Our immune system changes as we age. One part of ageing immunity is a gradual decline in the body’s ability to keep dormant viruses under control.

This is one reason shingles becomes more common in older adults. It is also why vaccination is recommended for older age groups and for some people with weakened immune systems.

The goal of vaccination is to remind and strengthen the immune system so that it is better able to keep the varicella-zoster virus suppressed.

What is Shingrix?

Shingrix is the newer shingles vaccine. It is a recombinant zoster vaccine, which means it is not a live virus vaccine. It contains a specific varicella-zoster virus protein combined with an immune-stimulating adjuvant to produce a strong immune response.

It is given as two doses, usually separated by several months.

The main purpose of Shingrix is to prevent shingles and its complications, especially post-herpetic neuralgia.

The CDC states that Shingrix is more than 90 percent effective at preventing shingles and post-herpetic neuralgia in adults aged 50 and older with healthy immune systems.

This high level of protection is one reason Shingrix has largely replaced the older shingles vaccine in many countries.

How is Shingrix different from the older Zostavax vaccine?

Before Shingrix, the best-known shingles vaccine was Zostavax.

Zostavax was a live attenuated vaccine, meaning it used a weakened form of the virus. It did reduce shingles risk, but its protection was more modest and tended to decline over time.

Shingrix is different in several important ways:

• it is not a live vaccine

• it produces a stronger immune response

• it has higher efficacy against shingles

• it gives better protection against post-herpetic neuralgia

• its protection appears to last longer

The CDC notes that Shingrix is preferred over the older live zoster vaccine because efficacy against shingles and post-herpetic neuralgia is higher, and because the protection from the older vaccine wanes substantially over time.

A review by the American Academy of Family Physicians reported that Shingrix is around 96 percent effective in adults aged 50 to 59 and 91 percent effective in adults aged 70 to 79, while Zostavax was about 51 percent effective at preventing shingles and 67 percent effective at preventing post-herpetic neuralgia.

In simple terms, both vaccines were designed to prevent shingles, but Shingrix is the more effective and more durable option.

Why are people talking about dementia?

The interest in shingles vaccination and dementia comes from a growing body of research suggesting that certain viral infections may influence brain health.

This does not mean that shingles “causes” Alzheimer’s disease in a simple, direct way. Alzheimer’s and other dementias are complex conditions influenced by age, genetics, vascular health, inflammation, metabolic factors, lifestyle, and many other variables.

However, the varicella-zoster virus is a virus that lives in nerve tissue. When it reactivates, it can cause inflammation in and around nerves. It is therefore biologically plausible that preventing reactivation might reduce some inflammatory or vascular stress on the nervous system.

That is the theory. The question is whether it holds up in real-world data.

What have the studies shown?

One widely discussed study, led by Stanford University and published in Nature, used an unusual vaccine eligibility policy in Wales as a kind of “natural experiment.”

In Wales, eligibility for the shingles vaccine depended on date of birth. People born just after a cut-off date were eligible, while those born just before it were not. This allowed researchers to compare groups that were very similar in age but differed in access to vaccination.

The study found that receiving the shingles vaccine was associated with a 20 percent relative reduction in the probability of a new dementia diagnosis over seven years.

Stanford Medicine described this as some of the strongest evidence so far that shingles vaccination may reduce dementia risk, while still recognising that further work is needed.

This finding has understandably attracted public attention. A recent article in The Times reported that private bookings for Shingrix had increased sharply after claims that the vaccine might help ward off dementia. The same article also made an important cautionary point: the dementia evidence remains unproven and is not yet based on the kind of randomised controlled trial that would be needed to confirm causation.

That caution matters.

A larger analysis of 6.3 million patient records in England has reportedly shown little evidence that eligibility for the live shingles vaccine reduced hospital-coded dementia. The University of Oxford has described this as a regression discontinuity analysis of 6.3 million individuals in England.

So, at present, the picture is interesting but not settled.

Some studies suggest a protective association. Others are less convincing. The strongest conclusion we can draw is not that the shingles vaccine definitely prevents dementia, but that the possibility is plausible enough to justify further research.

Observational studies versus clinical trials

This distinction is important.

Many of the dementia findings come from observational studies. These studies look at what happens in real-world populations. They can be very useful, especially when they involve large numbers of people.

But observational studies can be affected by bias.

For example, people who choose to be vaccinated may also be more likely to look after their health in other ways. They may attend doctors more regularly, manage blood pressure better, exercise more, or have better access to healthcare. These factors may themselves reduce dementia risk.

Researchers try to adjust for these differences, but they cannot always remove them completely.

The gold standard would be a randomised controlled trial, where similar people are randomly assigned to receive the vaccine or not, and then followed over time for dementia outcomes. According to The Times, such a trial is being run in Denmark, although results will not be available for several years.

Until then, we should be careful.

It is reasonable to say:

Shingles vaccination may be associated with a lower risk of dementia in some studies.

It is not yet reasonable to say:

Shingles vaccination definitely prevents Alzheimer’s disease.

Could Shingrix be more relevant than older shingles vaccines?

This is another interesting question.

Some of the strongest dementia-related data involve older shingles vaccine programmes, including the live vaccine used in Wales. Shingrix is newer, more immunogenic and more effective at preventing shingles itself.

It is therefore biologically plausible that Shingrix could have similar, or perhaps greater, relevance to brain health. But that remains to be proven.

For now, the best-established reason to have Shingrix is still the prevention of shingles and post-herpetic neuralgia.

Any possible reduction in dementia risk should be viewed as a potential additional benefit, not the primary reason to vaccinate.

Who should consider shingles vaccination?

Shingles vaccination is usually considered for adults aged 50 and over, although national recommendations vary by country and by health system.

It may be particularly worth discussing if you:

• are aged 50 or above

• have had shingles before

• are worried about post-herpetic neuralgia

• have a family history of dementia and are interested in sensible prevention strategies

• have medical conditions or medications that may affect immune function

• want to reduce your risk of a painful and potentially prolonged nerve condition

• In Hong Kong, Shingrix is generally accessed privately rather than through a broad government-funded shingles vaccination programme. The Government has acknowledged that shingles vaccines are available in the private healthcare market, but they are not currently part of a universal adult vaccination programme. In private practice, Shingrix may be considered for adults aged 50 and above, and for some adults aged 18 and above who are at increased risk of shingles because of immune suppression or other relevant medical factors. Suitability should be assessed individually, particularly for patients with complex medical conditions or those taking immune-modifying medication. (info.gov.hk)

What about side effects?

Shingrix is effective partly because it stimulates a strong immune response. That also means side effects are fairly common.

These may include:

• a sore arm

• redness or swelling at the injection site

• tiredness

• headache

• muscle aches

• fever or chills

• feeling generally unwell for a day or two

These symptoms usually settle quickly and are a sign that the immune system is responding.

Serious allergic reactions are rare, but anyone with a history of severe allergy to a vaccine component should seek medical advice before vaccination.

My view

I see shingles vaccination first and foremost as protection against shingles.

That alone is important. Shingles can be intensely painful, and post-herpetic neuralgia can significantly affect quality of life, particularly in older adults.

The possible link with dementia prevention is fascinating. It fits with a broader understanding that infections, inflammation, vascular health and immune ageing may all influence brain health over time.

But we must be careful not to overstate the evidence.

At present, I would not describe Shingrix as an Alzheimer’s vaccine. That would be premature and potentially misleading.

I would say this instead:

Shingrix is a highly effective shingles vaccine. It reduces the risk of shingles and its complications. Emerging observational evidence suggests that shingles vaccination may also be associated with a lower risk of dementia, but this has not yet been definitively proven in randomised clinical trials.

For many patients over 50, especially those who wish to reduce their risk of shingles and maintain long-term health, it is a vaccine worth discussing.

Sometimes prevention is not about one single outcome. It is about reducing several avoidable burdens as we age: pain, inflammation, complications, and possibly, though not yet proven, some element of longer-term neurological risk.

If you are interested in whether Shingrix is appropriate for you, please ask at your next appointment or contact the clinic for further advice.

Disclaimer: This article is intended for general information only and should not be taken as personal medical advice. Vaccine recommendations vary according to age, medical history, immune status, medication use and local guidelines. Please consult your doctor or healthcare provider before making any vaccination decision, especially if you are immunocompromised, pregnant, acutely unwell, have a history of severe allergic reaction, or have complex medical conditions.