A cure for Alzheimer's disease has been the great white whale of medical research, with numerous treatments showing promise in animals subsequently failing in clinical trails, while vaccine progress is slow. Several studies suggest we might have had a partial version under our noses for decades in the form of the influenza vaccine.
Rates of Alzheimer's disease and other forms of dementia are shooting upward as populations age in high and middle-income countries. Since advances like vaccination are one of the reasons older people are living long enough to get dementia, it might be expected that being vaccinated would be associated with a higher Alzheimer's risk. However, two years ago a study found the reverse, that vaccination is associated with lower rates of Alzheimer's in subsequent years.
Other small and medium-sized studies have found something similar, but the result is so surprising it has been tested on a much larger sample, and vindicated in the Journal of Alzheimer's Disease.
The study compared almost 936,000 people over the age of 65 who had been vaccinated against the flu between 2009 and 2015, with an identical number of the same demographic profile who had not. Four years later, 5.1 percent of the vaccinated group had been diagnosed with Alzheimer's, but the figure was 8.5 percent among the unvaccinated – vaccination was associated with 40 percent fewer cases.
However, in the absence of a confirmed chain of causation, the possibility some other factor is responsible can't be ruled out. The crucial question is whether vaccination is actually protecting the brain, or a confounding factor is responsible. Might a pre-diagnosis symptom of Alzheimer's be resistance to getting vaccinated, or being too disorganized to get to the doctor?
It would be hard to ethically justify a randomized control trial to determine this – those in the placebo arm would be at greater risk of influenza at least, and possibly Alzheimer's as well.
The authors attempted to address this by matching the patients in the two groups to be as similar as possible by demographics, consumption of other medications, and other conditions. Senior author Professor Paul Schulz of the University of Texas thinks this sufficient for confidence the vaccination is a cause of subsequent Alzheimer-free status, rather than a consequence of an initially clearer head.
“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," Schulz explained in a statement.
"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."
Support for this interpretation comes from the fact some of the other vaccines that appear to be protective are usually given much earlier in life. Adults getting booster shots for tetanus, diphtheria, and pertussis, for example also appear to have a lowered risk of Alzheimer's, yet probably made the decision long before the effects of the disease might show.
The period over which the study was run allowed the researchers to test whether annual vaccinations are more protective than a single shot at the start. Unsurprisingly, it seems they are, and the benefits wear off over the four-year period if not refreshed.
Not enough time has elapsed to test whether COVID-19 vaccination is similarly protective.