How a common vaccine might help safeguard your memory

Hi there,

I want to put in a plug for my other newsletter before getting to the topic that I want to talk about together. If you haven’t signed up for my free-flowing newsletter where I talk about everything other than science, please do so now. :-)

Now back to the focus of this newsletter.

If you're 50 and over, talk to your doctor about getting the shingles vaccine and not just to prevent the painful rash, but for a potential off-target effect: protection against dementia.

A compelling new study in Nature which I wrote a science column about this week shows that receiving the shingles vaccine reduced the probability of developing dementia by 20% over a seven-year period.

With dementia affecting crores of people worldwide and about 7.4% of adults over 60 (or 88 lakh people) in India, this finding could reshape how we approach brain health in aging populations.

What makes this research brilliantly powerful is its design: it was a natural experiment created by an arbitrary birthdate cutoff in the UK.

Those born on or after September 2, 1933, were eligible for the shingles vaccine, while those born even a day earlier were not. This created two nearly identical groups differing only in their likelihood of vaccination– a research setup as good as random assignment, but occurring naturally in real-world conditions.

In the current study, researchers tracked over 282,000 older adults, focusing on individuals born just one week on either side of the cutoff date. The analysis revealed a 3.5 percentage point reduction in new dementia diagnoses among the vaccinated group (equivalent to a 20% relative risk reduction).

The study focused on Zostavax, the older live-attenuated shingles vaccine, not the newer recombinant vaccine, Shingrix, which is now more widely used. However, a 2024 study in Nature Medicine found Shingrix was associated with a 17% increase in dementia-free survival time.

In India, both vaccines are approved and available.

So, what’s going on here?

The protective mechanism might involve reduced brain inflammation or "immune training." Previous studies have shown that vaccines for flu, tetanus-diphtheria, and pneumococcus also correlate with reduced dementia risk, suggesting that boosting immune function could be an undervalued strategy for preserving brain health.

The effect was also stronger among women, aligning with previous research showing live-attenuated vaccines often produce more robust immune responses in females.

A 20% reduction in dementia risk is nothing to scoff at and is potentially life-altering, equating to more time living independently, recognizing loved ones, and avoiding long-term care.

Natural experiments like this represent a scientific goldmine, often surpassing the vaunted "gold standard" randomized controlled trials (RCTs) in certain crucial ways.

Harvard physician-economist Anupam Jena, who commented on the study and has written extensively about natural experiments in his book Random Acts of Medicine, relies on "ingeniously devised natural experiments—random events that unknowingly turn us into experimental subjects" to reveal insights that would be impossible to discover through traditional research.

RCTs are often too short to detect effects that take years to manifest like dementia, which develops over decades. Natural experiments can span much longer timeframes because they analyze existing data. Second, it would be unethical in many cases to run a trial that exposes people to things like pollution. Third, RCTs typically study carefully selected populations under ideal conditions, while natural experiments capture real-world effectiveness across diverse populations.

Jena and his colleague Christopher Worsham have documented fascinating natural experiments across medicine: cardiac survival rates improve during national cardiology conferences when only the most specialized doctors remain on duty; babies born just before midnight have worse outcomes than those born just after due to staff shift changes; and even city marathons affect mortality rates for non-runners living along marathon routes due to delayed ambulance response times.

They also found children born in summer months are more likely to be diagnosed with ADHD than their slightly older classmates. These accidental experiments reveal insights impossible to capture through traditional research designs.

It’s worth picking up their book, and also looking into getting the shingles vaccine if you meet the criteria.

If there's one lesson here, it's that medical interventions often have effects far beyond their intended purposes. Sometimes, as with this vaccine, those effects can be remarkably positive.

Until next week, stay curious and healthy!

Anirban