So the basic problem that we usually have in observational data analyses for vaccines or other interventions is that we compare those who go get the vaccine to those who don’t get the vaccine. And we know vaccination behavior differs a lot between people and is related to all sorts of health behaviors, health motivation, dietary behaviors, physical activity levels, etc. And we just don’t have information in the data sources that we’re using for these analyses to be able to confidently adjust for all of these differences, which is why we never know what to make of these studies, whether they really reflect true cause and effect or just correlation...
So the basic problem that we usually have in observational data analyses for vaccines or other interventions is that we compare those who go get the vaccine to those who don’t get the vaccine. And we know vaccination behavior differs a lot between people and is related to all sorts of health behaviors, health motivation, dietary behaviors, physical activity levels, etc. And we just don’t have information in the data sources that we’re using for these analyses to be able to confidently adjust for all of these differences, which is why we never know what to make of these studies, whether they really reflect true cause and effect or just correlation. In the case of the shingles vaccine and how it was rolled out in several countries, it provides us with a unique opportunity to get at cause and effect in a much more convincing manner in a way that is very similar to a randomized clinical trial. So specifically, for example, in Wales, they said if you had your 80th birthday just prior to the start date of the program, which happened to be September 1st, 2013, you were ineligible and you remained ineligible for life. Well, if you had it just after, you were eligible. And so we’ve got this beautiful situation where we have got patient groups whose only difference is a few weeks in age, but who must be similar otherwise in all characteristics. Just like in a randomized trial, the control and intervention group should be similar in all characteristics because all that divides them is a coin toss. Here, all that divides them is whether they were born a few days earlier or a few days later. And we see in our data these large protective effects from shingles vaccination for new dementia diagnoses. That was our first paper that came out in Nature in April. Then we showed the same effect in Australia, another country that rolled out the vaccine in a similar way, in JAMA a few weeks later. And now, last week in Cell, we show that there’s not just an effect for dementia diagnosis, but also for new diagnosis of mild cognitive impairment among those who are cognitively unimpaired at the time of becoming eligible for vaccination. And among those who already have a dementia diagnosis at the time of becoming eligible for vaccination, there’s a large reduction in your probability of dying from dementia. So this really suggests that the vaccine may not just have preventive potential, but maybe even a therapeutic potential, which is very exciting. And we see these strong protective effects for dementia and dementia-related outcomes in data set after data set from different countries, different health systems, different types of data, and for different dementia-related outcomes. So this is a very compelling body of evidence that is coming out, always using these natural experiment approaches. We have another manuscript that will be published in the Lancet Neurology showing a similar effect in Canada and Ontario, which rolled out a vaccine, shingles vaccination, using date of birth cutoffs as well. So it’s a research agenda that we’re very excited about and that we keep building on. And I think it provides a picture of a convincing cause and effect relationship between shingles vaccination and dementia. So as a next step in this research, what we really think we need to conclusively test the link between shingles vaccination and dementia is a true randomized clinical trial of shingles vaccination for dementia prevention, ideally using the live attenuated shingles vaccine, which is off patent because that is the vaccine for which we have all this evidence from our natural experiments. There’s little commercial interest in this particular vaccine. So we’re hoping to raise these funds from foundations and philanthropy, because if this really is a true causal effect, then this would have huge implications for population health, for dementia care, and also for dementia research, for different causative factors of dementia and the dementia pathogenesis.
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