The root causes of dementia are still largely unclear, and the medical community
lacks highly effective preventive and therapeutic pharmaceutical agents for dementia
despite large investments into their development. There is growing interest in the
question if infectious agents play a role in the development of dementia, with
herpesviruses attracting particular attention. To provide causal as opposed to merely
correlational evidence on this question, we take advantage of the fact that in Wales
eligibility for the herpes zoster vaccine (Zostavax) for shingles prevention was
determined based on an individual’s exact date of birth. Those born before
September 2 1933 were ineligible and remained ineligible for life, while those born on or
after September 2 1933 were eligible to receive the vaccine. By using country-wide data on
all vaccinations received, primary and secondary care encounters, death certificates, and
patients’ date of birth in weeks, we first show that the percentage of adults who
received the vaccine increased from 0.01% among patients who were merely one week too old
to be eligible, to 47.2% among those who were just one week younger. Apart from this large
difference in the probability of ever receiving the herpes zoster vaccine, there is no
plausible reason why those born just one week prior to September 2 1933 should differ
systematically from those born one week later. We demonstrate this empirically by showing
that there were no systematic differences (e.g., in pre-existing conditions or uptake of
other preventive interventions) between adults across the date-of-birth eligibility
cutoff, and that there were no other interventions that used the exact same date-of-birth
eligibility cutoff as was used for the herpes zoster vaccine program. This unique natural
randomization, thus, allows for robust causal, rather than correlational, effect
estimation. We first replicate the vaccine’s known effect from clinical trials of
reducing the occurrence of shingles. We then show that receiving the herpes zoster vaccine
reduced the probability of a new dementia diagnosis over a follow-up period of seven years
by 3.5 percentage points (95% CI: 0.6 – 7.1, p=0.019), corresponding to a 19.9%
relative reduction in the occurrence of dementia. Besides preventing shingles and
dementia, the herpes zoster vaccine had no effects on any other common causes of morbidity
and mortality. In exploratory analyses, we find that the protective effects from the
vaccine for dementia are far stronger among women than men. Randomized trials are needed
to determine the optimal population groups and time interval for administration of the
herpes zoster vaccine to prevent or delay dementia, as well as to quantify the magnitude
of the causal effect when more precise measures of cognition are used. Our findings
strongly suggest an important role of the varicella zoster virus in the etiology of
dementia.