Lower Dementia Risk May Be Linked With Shingles Vaccine

The shingles vaccine may be linked with a 20% lower dementia risk, an analysis of 300,000 health records suggested.

Receiving the herpes zoster vaccine (Zostavax) reduced the probability of a new dementia diagnosis over 7 years by 3.5 percentage points (95% CI 0.6-7.1, P=0.019), reported Pascal Geldsetzer, MD, MPH, PhD, of Stanford University in California, and co-authors.

This corresponded to a 19.9% relative reduction in dementia risk, they said in a preprint paper on medRxiv, which has not yet been peer reviewed.

"The evidence provided by this study is fundamentally different to studies that have simply correlated -- with adjustment for, or matching on, certain covariates -- vaccine receipt with dementia," Geldsetzer told MedPage Today.

The unique way in which the zoster vaccine was rolled out in Wales constituted a natural experiment, he said.

In Wales, if you were born before Sept. 2, 1933, you couldn't get the zoster vaccine for shingles prevention and remained ineligible for life. If you were born on or after this date, you could get the shot.

This natural randomization may allow for a causal, rather than correlational, effect estimation, Geldsetzer suggested.

"This is a strong paper which supports the need of rigorous studies to determine the potential effect of HSV [herpes simplex virus] vaccination on dementia risk," observed epidemiologist Alberto Ascherio, MD, DrPH, of the Harvard T.H. Chan School of Public Health in Boston, who is known for his work linking the Epstein-Barr virus and multiple sclerosis.

"More broadly, this paper strengthens the evidence that infections could be important risk factors for dementia, and that other vaccines could have protective effects," Ascherio told MedPage Today.

"Although it is not definitive, mostly because its results could have occurred by chance, it stands out from previous investigations for having eliminated the most common source of bias -- namely, that individuals who choose to be vaccinated tend to be healthier than those unvaccinated," he added.

In several studies, viruses have been linked with subsequent dementia and other neurodegenerative diseases. Human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) have been found in postmortem tissue samples of people with Alzheimer's disease at levels up to twice as high as non-Alzheimer's samples. And some researchers have suggested that HSV-1 coupled with an APOE4 gene ups Alzheimer's risk considerably.

Geldsetzer and colleagues looked at 282,541 adults born from Sept. 1, 1925 to Aug. 31, 1942 who were registered with a primary care provider when the zoster vaccine program in Wales started on Sept. 1, 2013. People who received a dementia diagnosis before Sept. 1, 2013 were excluded.

People born from Sept. 2, 1933 to Sept. 1, 1934 became eligible for the zoster vaccine on Sept. 1, 2013. Eligibility was progressively extended to younger age cohorts each year, based on their date of birth.

These eligibility requirements led to an abrupt shift in vaccination uptake. Being born just one week after Sept. 2, 1933 raised the probability of ever receiving the zoster vaccine from 0.01% to 47.2% (P<0.001).

Being eligible for the zoster vaccine led to a 1.3-percentage point (95% CI 0.2-2.7, P=0.022) absolute reduction in the probability of a new dementia diagnosis during a 7-year follow-up period. Considering that not all people who were eligible received the vaccine, the researchers determined that actually receiving the zoster shot reduced the probability of a new dementia diagnosis by 3.5 percentage points (95% CI 0.6-7.1, P=0.019).

Because shingles is more common among women than men -- and because the pathogenesis of dementia may differ by sex -- the researchers looked at subgroup differences and found the vaccine's effect on new dementia diagnoses was greater among women than men.

"In fact, among men, the point estimates were close to zero across all specifications," Geldsetzer and co-authors noted. The protective effect was significantly stronger for women than men for Alzheimer's disease (P=0.018), but not for vascular dementia (P=0.376), they added.

Randomized trials are needed to confirm the findings and uncover more details about vaccine timing and frequency, Geldsetzer and colleagues said.

The research had several limitations, they acknowledged. Follow-up was limited to a maximum period of 8 years. Data from people ages 79 to 80 were weighted most heavily in regression analyses. Only Zostavax was evaluated in the study; the newer recombinant subunit zoster vaccine (Shingrix) was not available in the U.K. until September 2021.

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