Most of us carried the chickenpox virus through childhood and thought little of it again. But scientists are now uncovering an uncomfortable truth: that dormant virus, hidden in nerve cells for decades, may be slowly damaging our brains as we age.
Shingles is caused by the varicella-zoster virus, the same virus that causes chickenpox. After people contract chickenpox, usually in childhood, the virus stays dormant in the nerve cells for life. In people who are older or have weakened immune systems, the dormant virus can reactivate and cause shingles. Yet emerging evidence suggests the consequences of that reactivation extend far beyond the painful rash. Findings strongly implicate VZV reactivation as a modifiable risk factor for dementia.
The mechanism appears to be multifaceted. Clinical and subclinical reactivations of the neurotropic herpesvirus may constitute a chronic immune stressor that drives inflammatory pathways in both the peripheral and central nervous system. The varicella zoster virus has also recently been linked to amyloid deposition and aggregation of tau proteins, as well as cerebrovascular disease that resembles the patterns commonly seen in Alzheimer's disease. In essence, the virus doesn't merely cause a skin infection; it may trigger the very biochemical changes associated with cognitive decline.
The most compelling evidence for prevention comes from an unusual natural experiment in Wales. The vaccination program, which began September 1, 2013, specified that anyone who was 79 on that date was eligible for the vaccine for one year. People who were 80 or older on September 1, 2013, were out of luck. These rules, designed to ration limited vaccine supply, meant that the slight difference in age between 79- and 80-year-olds made all the difference in who had access to the vaccine.
This arbitrary cutoff created an ideal research scenario. Researchers analyzing the health records of Welsh older adults discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine. The remarkable findings, published April 2 in Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia. Researchers later confirmed similar patterns in Australian health data, lending weight to the finding.
More striking still, the protection appears not merely preventive but therapeutic. In a follow-up study published December 2 in Cell, the researchers found that the vaccine may also benefit those already diagnosed with dementia by slowing the progress of the disease. Of the 7,049 Welsh seniors who had dementia at the start of the vaccination program, nearly half died from dementia during the follow-up period; but among those who'd been vaccinated, only about 30 percent died from dementia.
The effect proved strongest in women. Protection against dementia was much more pronounced in women than in men. This could be due to sex differences in immune response or in the way dementia develops. Women on average have higher antibody responses to vaccination, and shingles is more common in women than in men.
A crucial limitation warrants acknowledgement: most evidence concerns the older live-attenuated vaccine, which is now discontinued in the United States and most Western countries in favour of newer recombinant formulations. The recombinant vaccine is associated with a significantly lower risk of dementia within the next 6 years. Receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.
For Australian readers, the stakes merit attention. Researchers also analysed similar health records in Australia, which has a similar shingles vaccination program as Wales. Dementia represents one of the nation's fastest-growing health challenges, particularly with an ageing population. If the protective signal holds in subsequent clinical trials, widespread vaccination could alter the trajectory of cognitive decline in older Australians.
Whether the vaccine protects against dementia by revving up the immune system overall, by specifically reducing reactivations of the virus or by some other mechanism is still unknown. Also unknown is whether a newer version of the vaccine, which contains only certain proteins from the virus and is more effective at preventing shingles, may have a similar or even greater impact on dementia. Researchers at Stanford and elsewhere are now pursuing larger randomised trials to confirm these findings and clarify mechanism.
The puzzle is not yet solved. We'll need additional studies to confirm the benefit. Scientists also want to understand other details of the vaccine's effect, such as whether protection applies more to some types of dementia than others, and whether the effect of vaccination changes over time. For now, the evidence points toward a simple prevention that may also treat existing disease: a vaccine developed to prevent a painful rash might do far more than expected.