Herpesviruses that affect the nervous system are thought to play a role in the development of dementia. One way to combat these viruses is through vaccination. However, vaccines—particularly live attenuated ones—can trigger a broad immune response and may cause significant side effects. Moreover, immune responses to vaccines often differ between men and women.
In most studies assessing the effect of vaccination on dementia risk, researchers compared people who received the vaccine with those who did not. However, this approach can be flawed due to numerous confounding factors—variables other than vaccination that may influence the risk of dementia and are difficult to control fully.
In Wales, eligibility for the shingles vaccine was determined by birth date. Those born before September 2, 1933, were not eligible to receive the vaccine, while those born on or after that date were.
People born just a few weeks apart are unlikely to differ significantly in terms of health status, education, or access to medical care, which means the comparison groups were highly comparable. Such a natural experiment allowed researchers to minimize hidden biases and draw more reliable conclusions.
The vaccine used in the study was Zostavax, a live attenuated shingles vaccine. The newer recombinant subunit vaccine, Shingrix, became available in the UK only after the study period had ended.
First, the researchers confirmed that the vaccine effectively reduced the risk of developing shingles, as had been demonstrated in clinical trials. Then, they found that it also reduced the risk of developing dementia by about 20% over seven years of follow-up. The vaccine did not appear to affect the risk of other diseases or lead to greater use of different vaccines or preventive care.
Shingles vaccine reduces dementia risk more in women than in men
This difference is understandable. For one, dementia tends to be less common in older men, making any statistical effect harder to detect. For another, women are known to have stronger immune responses to vaccines and often derive more benefits, especially from live attenuated vaccines. Additionally, men and women differ both in how their immune systems respond to vaccination and in the biological mechanisms underlying dementia.
How the shingles vaccine might protect against dementia: protective mechanisms
Understanding how the varicella-zoster virus (VZV)—the cause of shingles—might be linked to dementia is key. Research suggests that reactivation of VZV can lead to neuroinflammation, damage to blood vessels in the brain, and accumulation of amyloid and tau proteins—all of which are associated with Alzheimer’s disease.
VZV reactivation has been linked to a higher risk of dementia. One study showed that people who experienced multiple episodes of shingles had a greater likelihood of developing dementia. Antiviral treatment during a shingles outbreak was associated with a reduced risk of dementia.
There is also a hypothesis that decreasing VZV activity after vaccination might reduce the activity of herpes simplex virus type 1 (HSV-1) in the brain. Furthermore, the study found that the vaccine’s protective effect was stronger among those who had not recently received a flu vaccine. Protection was also more pronounced in individuals without autoimmune or allergic diseases. These findings suggest that a general immune response—beyond just targeting VZV—may play an important role.
Both mechanisms—viral suppression and broader immune modulation—may be acting in tandem.
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A natural experiment on the effect of herpes zoster vaccination on dementia
