A large new study tracking the health of around two million people has found annual influenza vaccination is associated with a significantly lower risk of developing Alzheimer’s disease. The compelling findings build on growing research finding links between several viral infections and neurodegenerative disease.
Over the last few years several small studies have pointed to unexpected links between influenza vaccination and lowered Alzheimer’s risk. This new research offers the largest and most robust investigation to date into the unusual correlation and also presents some novel hypotheses as to how the humble flu vax could be lowering a person’s chances of developing Alzheimer’s.
The study looked at health record data from several million Americans over the age of 65. A cohort of around 930,000 flu-vaccinated subjects was matched against a similar-sized cohort of unvaccinated subjects.
Across a period of around six years the researchers saw 5.1 percent of flu-vaccinated subjects develop Alzheimer’s disease, compared to 8.5 percent developing the disease in the unvaccinated group. The researchers calculated a 40-percent reduction in Alzheimer’s risk for subjects over the age of 65 receiving annual flu vaccinations for at least four years.
“We found that flu vaccination in older adults reduces the risk of developing Alzheimer’s disease for several years,” noted first author Avram Bukhbinder. “The strength of this protective effect increased with the number of years that a person received an annual flu vaccine – in other words, the rate of developing Alzheimer’s was lowest among those who consistently received the flu vaccine every year.”
So perhaps the million-dollar question is how could the flu vaccine be preventing, or slowing, the onset of Alzheimer’s disease?
Senior author on the new research Paul Schulz said he doesn’t think this association between the flu vaccine and Alzheimer’s risk is intrinsically related to the flu vaccine. Instead, he suspects the mechanism at play may have something to do with what vaccines in general do to the innate immune system.
“Since there is evidence that several vaccines may protect from Alzheimer's disease, we are thinking that it isn't a specific effect of the flu vaccine,” explained Schulz. “Instead, we believe that the immune system is complex, and some alterations, such as pneumonia, may activate it in a way that makes Alzheimer's disease worse. But other things that activate the immune system may do so in a different way – one that protects from Alzheimer's disease. Clearly, we have more to learn about how the immune system worsens or improves outcomes in this disease.”
The idea is known as “trained immunity” and it suggests vaccination can induce a number of non-specific immune changes beyond the specific antigen targeted by an individual vaccine. This could explain how a variety of different vaccines, from tetanus to tuberculosis, have all been associated with lower rates of dementia.
But there also is another hypothesis that could explain the new findings. One of the most interesting emerging ideas in Alzheimer’s research involves the role infectious diseases may play in the progression of neurodegenerative disease.
Back in the 1950s many scientists referred to neurodegenerative conditions such as Alzheimer’s by the name “slow virus diseases.” The idea was viral infections can quietly result in the destruction of brain cells for years, or even decades, after the acute infection. For Alzheimer’s the leading viral contender was suspected to be herpes.
Around the 1980s this idea fell out of favor, replaced by more modern hypotheses focusing on toxic proteins accumulating and causing neurodegenerative disease. But recently the old viral idea has been rekindled, as researchers found a number of relationships between viral infections and diseases such as Alzheimer’s, Parkinson’s and multiple sclerosis.
Several mechanisms could explain how viruses influence neurodegeneration but the most commonly floated hypothesis is that viral infections can trigger an excessive immune response that leads to a cascade of events, culminating in neuroinflammation that contributes to the development of a variety of diseases. In the case of the influenza vaccine, it may be possible that simply preventing a bout of flu in one’s senior years can make a significant difference to the likelihood of Alzheimer’s developing.
An even more interesting hypothesis suggested in the study is that flu vaccination protects directly against Alzheimer’s because of a structural similarity between proteins generated by the influenza virus and the toxic amyloid proteins suspected as causing neurodegeneration. This “epitopic similarity” means it is possible the immune response generated by a flu vaccine helps prevent the development of Alzheimer’s.
Of course, there is a lot of speculation here, and the researchers are clear it will be critical for future studies to investigate exactly what mechanisms could be at play. What is increasingly apparent, however, is that there certainly seems to be a link between viral infection and neurological disease, and vaccination may mitigate some of that impact. Recent research revealing the impact of COVID-19 on the brain only builds on this general idea.
“It will be critical for future investigations to clarify which mechanisms underlie the apparent effect of flu vaccination on AD risk, whether age at vaccination moderates the vaccine’s association with AD risk, and whether influenza vaccination also affects rate of progression in patients with MCI [Mild Cognitive Impairment] or AD,” the new study concludes.
The new study was published in the Journal of Alzheimer’s Disease.
Source: UTHealth Houston