A shot of a shingles vaccine blocks reactivation, potentially preventing the virus from triggering brain inflammation that could contribute to the development of dementia. Conversely, there’s some evidence that having shingles may increase the risk of dementia.

A possible mechanism

But not every vaccine linked to reduced dementia risk comes with such an explanation for how it may protect the brain. For example, the seasonal flu vaccine seems to reduce dementia, but it’s unclear how. Still, in a large retrospective study published last month, researchers again bolstered the link between the seasonal flu shot and lower risks of dementia, this time finding that high-dose seasonal flu shots given to older patients are yet more protective against dementia than standard doses.

In other words, there seems to be a dose-dependent response—the higher the flu vaccine dose, the lower the dementia risk. The authors don’t speculate on how the seasonal shot could affect cognitive health, but they call for more research into potential mechanisms, including trained immunity.

In the March hypothesis piece, published in the journal Frontiers in Immunology, Devine and colleagues hypothesize that trained immunity from vaccinations could indeed be responsible.

“A central element in this immunological model is that uncontrolled or excessive levels of neuro-inflammation, associated with elevated dementia risk, can be counteracted by epigenetic reprogramming of innate immune cells,” they write.

For instance, it may be that the nonspecific changes to innate responses from vaccines are able to keep both targeted and non-targeted pathogens in check, preventing brain inflammation from flaring up, they say.

For now, the idea is just a hypothesis, and there’s a lot more work needed to validate it. But the stakes are high for pursuing it, the researchers argue. “Elucidating the mechanisms underlying these promising observations may open new avenues to promote healthy aging through vaccination and could be crucial for alleviating the global burden of dementia,” they write.