Herpes Zoster, Shingles Vaccine May Reduce Dementia Risk in Older Adults

Receipt of the live-attenuated herpes zoster vaccine is associated with a significantly reduced risk of developing dementia, according to the findings of a study published in Nature.

Researchers sought to determine whether a causal link exists between zoster vaccination and the incidence of dementia, moving beyond prior studies that only identified correlations.

The researchers conducted a quasi-experimental study utilizing a regression discontinuity design. They analyzed electronic health records obtained from the Secure Anonymised Information Linkage Databank in Wales. Adults born between September 1, 1925, and September 1, 1942, and free of dementia at the start of the zoster vaccination program in 2013, were included. The program’s structure made individuals born on or after September 2, 1933, eligible for the vaccine, while those born before that date were not.

Vaccination uptake increased sharply at this eligibility threshold, from just 0.01% among those born 1 week prior to the cutoff to 47.2% in those born 1 week after, providing an ideal setting for comparing dementia outcomes between otherwise similar groups. For the study, the researchers analyzed a total of 282,541 older adults. Baseline characteristics, including past medical history, use of preventive health services, and education levels, were balanced on either side of the cutoff, supporting the assumption of comparability.

Over a 7-year follow-up period, 35,307 participants were newly diagnosed with dementia. Using a 2-stage least squares regression, the researchers estimated that receiving the zoster vaccine reduced the probability of a new dementia diagnosis by 3.5 percentage points (95% CI, 0.6 to 7.1; P =.019), a relative reduction of 20% (95% CI, 6.5 to 33.4).

This protective effect was consistently observed across various analytical methods and remained strong, even after accounting for differences in follow-up duration, adjustments for clinical factors, and the frequency of health care visits. This benefit was more pronounced in women than men and was consistent across various sensitivity analyses, including alternate definitions of dementia and models adjusting for healthcare utilization and preexisting conditions. Secondary analyses also confirmed reductions in shingles and postherpetic neuralgia, reinforcing the biological plausibility of the findings.

The study successfully replicated its findings using death certificate data from England and Wales, confirming a lower rate of dementia-related deaths in vaccine-eligible cohorts. These results suggest that herpes zoster vaccination may offer long-term cognitive protection in addition to its intended role in preventing shingles.

The study was limited by potential under-diagnosis or delays in dementia detection, lack of generalizability beyond the 79 to 80 age range, and an inability to assess the impact of the newer recombinant zoster vaccine.

“…[O]ur exploratory analyses on the effect mechanism that links zoster vaccination to dementia suggest that both a mechanism through reducing clinical and subclinical reactivations of [varicella zoster virus] as well as a pathogen-independent immune mechanism are plausible,” the researchers concluded.